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Systemic Lupus Erythematosus: HELP
Articles from Puerto Rico
Based on 27 articles published since 2009
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These are the 27 published articles about Lupus Erythematosus, Systemic that originated from Puerto Rico during 2009-2019.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Multifocal osteonecrosis in systemic lupus erythematosus: case report and review of the literature. 2013

Fajardo-Hermosillo, Luis D / López-López, Linnette / Nadal, Anaida / Vilá, Luis M. ·Department of Medicine, Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. ·BMJ Case Rep · Pubmed #23595183.

ABSTRACT: Osteonecrosis is a relatively common comorbidity in systemic lupus erythematosus (SLE), but avascular necrosis in multiple sites is unusual. Multifocal osteonecrosis is defined as osteonecrotic lesions affecting three or more separate anatomic sites. We report a case of a 24-year-old woman diagnosed with SLE when she presented with mucocutaneous, haematological and mild renal manifestations. Initially, she was treated with prednisone and hydroxychloroquine and her condition remained stable. Two years later, she developed severe bilateral pretibial ulcers intractable to immunosuppressive therapy and broad-spectrum antibiotics. MRI of both legs disclosed osteonecrosis of the distal tibia, proximal tibia, distal fibula and talus bilaterally. She had elevated anticardiolipin antibodies for which she was treated with chronic anticoagulation resulting in complete healing of the leg ulcers and no further episodes of osteonecrosis. In addition to this case, we review the demographic, clinical and pharmacological features of 14 cases reported in the literature.

2 Article Remission and low disease activity state (LDAS) are protective of intermediate and long-term outcomes in SLE patients. Results from LUMINA (LXXVIII), a multiethnic, multicenter US cohort. 2019

Alarcón, G S / Ugarte-Gil, M F / Pons-Estel, G / Vilá, L M / Reveille, J D / McGwin, G. ·1 The University of Alabama at Birmingham, Birmingham, USA. · 2 Universidad Peruana Cayetano Heredia, Lima, Perú. · 3 Hospital Guillermo Almenara, EsSalud, Lima, Perú. · 4 Universidad Científica del Sur, Lima, Perú. · 5 Hospital Provincial de Rosario, Rosario, Argentina. · 6 Grupo Oroño-Centro Regional de Enfermedades Autoinmunes y Reumáticas (GO-CREAR), Sanatorio Parque Rosario, Santa Fe, Argentina. · 7 University of Puerto Rico Medical Sciences Campus, San Juan, USA. · 8 The University of Texas Health McGovern Medical School, Houston, USA. ·Lupus · Pubmed #30678605.

ABSTRACT: OBJECTIVE: The objective of this report is to determine the impact of remission and low disease activity state (LDAS) on damage accrual and mortality in systemic lupus erythematosus (SLE) patients. PATIENTS AND METHODS: Visits from the Lupus in Minority populations: Nature vs. Nurture (LUMINA) cohort were categorized into remission (Systemic Lupus Activity Measure (SLAM) score = 0 and prednisone ≤ 5 mg/day and no immunosuppressants), LDAS ((not on remission), SLAM score ≤ 3, prednisone ≤ 7.5 mg/day, no immunosuppressants), or neither: active. Remission and LDAS visits were combined because of the relatively small number of remission visits. Their impact on damage accrual and mortality were examined by Poisson and logistic multivariable regressions adjusting for variables known to affect these outcomes. RESULTS: A total of 3879 visits for 558 patients (28% Caucasian, 37% African descent, 35% Hispanic) were studied. These visits corresponded to 71 in remission, 585 in LDAS, and 3223 active. The longer the percentage of time the patients were in remission/LDAS, the less damage accrual observed (rate ratio 0.1773 (95% confidence interval (CI) 0.1216 to 0.2584) p < 0.0001). A trend was observed in terms of mortality although statistical significance was not reached (odds ratio 0.303 (95% CI 0.063 to 1.456), p = 0.1360). CONCLUSIONS: The longer the patient's state on Remission/LDAS, the less damage accrual that occurs. The protective effect on mortality was not statistically significant.

3 Article Transancestral mapping and genetic load in systemic lupus erythematosus. 2017

Langefeld, Carl D / Ainsworth, Hannah C / Cunninghame Graham, Deborah S / Kelly, Jennifer A / Comeau, Mary E / Marion, Miranda C / Howard, Timothy D / Ramos, Paula S / Croker, Jennifer A / Morris, David L / Sandling, Johanna K / Almlöf, Jonas Carlsson / Acevedo-Vásquez, Eduardo M / Alarcón, Graciela S / Babini, Alejandra M / Baca, Vicente / Bengtsson, Anders A / Berbotto, Guillermo A / Bijl, Marc / Brown, Elizabeth E / Brunner, Hermine I / Cardiel, Mario H / Catoggio, Luis / Cervera, Ricard / Cucho-Venegas, Jorge M / Dahlqvist, Solbritt Rantapää / D'Alfonso, Sandra / Da Silva, Berta Martins / de la Rúa Figueroa, Iñigo / Doria, Andrea / Edberg, Jeffrey C / Endreffy, Emőke / Esquivel-Valerio, Jorge A / Fortin, Paul R / Freedman, Barry I / Frostegård, Johan / García, Mercedes A / de la Torre, Ignacio García / Gilkeson, Gary S / Gladman, Dafna D / Gunnarsson, Iva / Guthridge, Joel M / Huggins, Jennifer L / James, Judith A / Kallenberg, Cees G M / Kamen, Diane L / Karp, David R / Kaufman, Kenneth M / Kottyan, Leah C / Kovács, László / Laustrup, Helle / Lauwerys, Bernard R / Li, Quan-Zhen / Maradiaga-Ceceña, Marco A / Martín, Javier / McCune, Joseph M / McWilliams, David R / Merrill, Joan T / Miranda, Pedro / Moctezuma, José F / Nath, Swapan K / Niewold, Timothy B / Orozco, Lorena / Ortego-Centeno, Norberto / Petri, Michelle / Pineau, Christian A / Pons-Estel, Bernardo A / Pope, Janet / Raj, Prithvi / Ramsey-Goldman, Rosalind / Reveille, John D / Russell, Laurie P / Sabio, José M / Aguilar-Salinas, Carlos A / Scherbarth, Hugo R / Scorza, Raffaella / Seldin, Michael F / Sjöwall, Christopher / Svenungsson, Elisabet / Thompson, Susan D / Toloza, Sergio M A / Truedsson, Lennart / Tusié-Luna, Teresa / Vasconcelos, Carlos / Vilá, Luis M / Wallace, Daniel J / Weisman, Michael H / Wither, Joan E / Bhangale, Tushar / Oksenberg, Jorge R / Rioux, John D / Gregersen, Peter K / Syvänen, Ann-Christine / Rönnblom, Lars / Criswell, Lindsey A / Jacob, Chaim O / Sivils, Kathy L / Tsao, Betty P / Schanberg, Laura E / Behrens, Timothy W / Silverman, Earl D / Alarcón-Riquelme, Marta E / Kimberly, Robert P / Harley, John B / Wakeland, Edward K / Graham, Robert R / Gaffney, Patrick M / Vyse, Timothy J. ·Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA. · Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA. · Divisions of Genetics and Molecular Medicine and Immunology, Infection and Inflammatory Diseases, King's College London, Guy's Hospital, London SE1 9RT, UK. · Arthritis &Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA. · Center for Human Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA. · Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA. · Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA. · Division of Clinical Immunology and Rheumatology, UAB School of Medicine, Birmingham, Alabama 35294, USA. · Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala 752 36, Sweden. · Departamento de Reumatología, Hospital G. Almenara y Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima 15081, Perú. · Hospital Italiano de Córdoba, Córdoba X5004BAL, Argentina. · Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico. · Department of Clinical Sciences, Rheumatology, Lund University, Lund 22362, Sweden. · Hospital Eva Perón, Granadero Baigorria S2152EDD, Argentina. · Department of Internal Medicine and Rheumatology, Martini Hospital, Van Swietenplein 1, 9728, NT, Groningen, The Netherlands. · Division of Rheumatology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati, Cincinnati, Ohio 45229, USA. · Centro de Investigación Clínica de Morelia, Morelia, Michoacán 58070, Mexico. · Hospital Italiano de Buenos Aires, 1181, Buenos Aires C1181ACH, Argentina. · Department of Autoimmune Diseases, Hospital Clínic, University of Barcelona, Barcelona, Catalonia 08007, Spain. · Department of Public Health and Clinical Medicine, Division of Rheumatology, Umeå University, Umeå 901 87, Sweden. · Department of Health Sciences and Institute of Research in Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara 28100, Italy. · Unidade Multidisciplinar em Investigação Biomédica/Instituto de Ciências Biomédicas de Abel Salazar-Universidade do Porto, Porto 4099-003, Portugal. · Department of Rheumatology, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria 35010, Spain. · Division of Rheumatology, Department of Medicine (DIMED), University of Padua, Padua 35122, Italy. · Department of Pediatrics and Child Health Center, Albert Szent-Györgyi Medical Center, Faculty of Medicine, University of Szeged, Szeged H-6720, Hungary. · Hospital Universitario 'Dr José Eleuterio González' Universidad Autonoma de Nuevo León, Monterrey 64020, México. · CHU de Québec Université Laval, Québec, Canada G1R 2JG. · Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27101, USA. · Institute of Environmental Medicine, Unit of Immunology and Chronic diseases, Karolinska Institutet, Stockholm 171 77, Sweden. · Division of Rheumatology, Hospital Interzonal General de Agudos General San Martín, La Plata 1900, Argentina. · University of Guadalajara, Departamento de Fisiología, Guadalajara, Jalisco 44100, Mexico. · Centre for Prognosis Studies in The Rheumatic Diseases, Krembil Research Institute, Toronto Western Hospital, Toronto, Ontario M5T 2S8, Canada. · Unit of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm SE-171 76, Sweden. · Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. · Department of Rheumatology and Clinical Immunology,University Medical Center Groningen,University of Groningen, Groningen 9713 GZ, The Netherlands. · Department of Immunology, University of Texas SouthWestern Medical Center, Dallas, Texas 75235, USA. · Department of Pediatrics, Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. · Department of Rheumatology, Albert Szent-Györgyi Medical Centre, University of Szeged, Szeged H-6720, Hungary. · Department of Rheumatology, Odense University Hospital, Odense 5000, Denmark. · Rheumatology, Cliniques Universitaires Saint-Luc &Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Louvain-la-Neuve 1348, Belgium. · Hospital General de Culiacán, Sinaloa 80220, Mexico. · Instituto de Parasitología y Biomedicina López Neyra, CSIC, Granada 18100, Spain. · University of Michigan Medical Center, Ann Arbor, Michigan 48103, USA. · Centro de Estudios Reumatológicos, Santiago de Chile, Santiago 7500000, Chile. · Departamento de Reumatología, Hospital General de México, Mexico D.F., Mexico. · Department of Rheumatology, Mayo Clinic, Rochester, Minnesota 94158, USA. · Instituto Nacional de Medicina Genómica (INMEGEN), México City 14610, México. · Unidad de Enfermedades Autoimmunes Sistémicas, UGC Medicina Interna, Hospital Universitario San Cecilio, Granada 18007, Spain. · Division of Rheumatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218, USA. · Rheumatology Division, McGill University, Montreal, Quebec H3A 0G4, Canada. · Department of Rheumatology, Sanatorio Parque, Rosario S2000, Argentina. · University of Western Ontario, London, Ontario, Canada M5T 2S8. · Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. · The University of Texas Health Science Center at Houston (UTHealth) Medical School, Houston, Texas 77030, USA. · Hospital Universitario Virgen de las Nieves, Granada 18014, Spain. · Instituto Nacional de Ciencias Médicas y Nutrición, Department of Endocrinology and Metabolism, Vasco de Quiroga 15, Mexico City 14080, Mexico. · Unidad Reumatología y Enfermedades Autoinmunes H.I.G.A. Dr Alende Mar del Plata, Buenos Aires B7600, Argentina. · Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca'Granda Ospedale Ma Repiore Policlinico and University of Milan, Milan 20122, Italy. · Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, California 95616, USA. · Rheumatology Division of Neuro and Inflammation Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping 581 83, Sweden. · Ministry of Health, San Fernando del Valle de Catamarca, Catamarca K4700, Argentina. · Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund 221 00, Sweden. · Unidad de Biología Molecular y Medicina Genómica Instituto de Investigaciones Biomédicas/UNAM Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico. · Hospital Santo Antonio, Universidade do Porto, Porto 4099-003, Portugal. · University of Puerto Rico School of Medicine, San Juan 00936, Puerto Rico. · Department of Medicine, Cedars Sinai Medical Center, Los Angeles, California 90048, USA. · Human Genetics, Genentech Inc, South San Francisco, California 94080, USA. · Department of Neurology and Institute of Human Genetics, University of California at San Francisco, San Francisco, California 94158, USA. · Université de Montréal and the Montreal Heart Institute, Montreal, Quebec, Canada H1T 1C8. · Center for Genomics &Human Genetics, The Feinstein Institute for Medical Research, Manhasset, New York 11030, USA. · Department of Medical Sciences, Rheumatology, Uppsala University, 752 36, Sweden. · Rosalind Russell/Ephraim P Engleman Rheumatology Research Center, Division of Rheumatology, UCSF School of Medicine, San Francisco, California 94158, USA. · Keck School of Medicine of USC, Los Angeles, California 90033, USA. · Department of Pediatrics, Duke University, Durham, North Carolina 27708, USA. · Department of Pediatrics and the Institute of Medical Sciences, The Hospital for Sick Children, Hospital for Sick Children Research Institute and University of Toronto, Ontario, Canada M5G 1X8. · Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research (GENYO), Granada 18007, Spain. · Unit of Institute of Environmental Medicine, Karolinska Institute, Solnavägen 171 77, Sweden. ·Nat Commun · Pubmed #28714469.

ABSTRACT: Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10

4 Article A unique antiphospholipid assay recognizing phospholipid mixture compared with criteria antiphospholipid immunoassays in lupus patients. 2017

Zuo, Y / Willis, R / Papalardo, E / Petri, M / Harris, E N / Schleh, A / DeCeulaer, K / Smikle, M / Vilá, L M / Reveille, J D / Alarcón, G S / Gonzalez, E B. ·1 University of Texas Southwestern Medical Center, Texas, USA. · 2 University of Texas Medical Branch, Galveston, Texas, USA. · 3 John Hopkins University School of Medicine, Baltimore, Maryland, USA. · 4 University of the West Indies, Mona Campus, Kingston, Jamaica. · 5 Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. · 6 University of Texas School of Medicine at Houston, Texas, USA. · 7 University of Alabama at Birmingham, Alabama, USA. ·Lupus · Pubmed #27753626.

ABSTRACT: Background While essential for the classification of antiphospholipid syndrome (APS), anticardiolipin (aCL) assays lack specificity and anti-β2glycoproteinI (anti-β2GPI) assays lack sensitivity in this regard. Our aim was to perform a comparative analysis of the APhL ELISA assay (IgG/IgM) and criteria antiphospholipid (aPL) immunoassays in identifying APS-related clinical manifestations in a large group of patients with systemic lupus erythematosus (SLE). Methods Serum samples from 1178 patients from the Hopkins ( n = 543), LUMINA ( n = 588) and Jamaican SLE cohorts ( n = 47) were examined for IgG/IgM positivity in aCL (in-house), anti-β2GPI (two commercial kits) and APhL (Louisville APL) ELISA assays. Correlation of assay positivity with clinical manifestations and sensitivity, specificity, positive and negative predictive values and likelihood ratios were evaluated. A case series analysis was also performed in patients for whom there was isolated positivity in the specific aPL assays. Results The prevalence of aCL positivity was 34.9%, anti-β2GPI kit A was 22.6%, APhL was 11.5% and anti-β2GPI kit B was 7.6% in the study population. Anti-β2GPI kit B, aCL and APhL assays were correlated with venous thrombosis, while only APhL was significantly correlated with arterial thrombosis and consistently correlated with pregnancy-related morbidity. No significant correlations were noted for anti-β2GPI kit A. Sensitivity was greatest for aCL assays followed by anti-β2GPI kit A, APhL and anti-β2GPI kit B, while specificity was greatest and equal for anti-β2GPI kit B and APhL assays. Conclusions Overall, APhL antibodies, especially IgG, represent a promising biomarker for the classification of APS patients in the context of autoimmunity and in risk assessment with regards to pregnancy morbidity and thrombotic manifestations.

5 Article Factors associated with disease expression patterns in systemic lupus erythematosus patients: results from LUMINA (LXXVII), a multiethnic US cohort. 2017

Ugarte-Gil, M F / Pimentel-Quiroz, V R / Vilá, L M / Reveille, J D / McGwin, G / Alarcón, G S. ·1 Servicio de Reumatología, Hospital Nacional Guillermo Almenara Irigoyen, EsSalud, Lima, Perú. · 2 Universidad Científica del Sur, Lima, Perú. · 3 Department of Internal Medicine, Division of Rheumatology, University of Puerto Rico, San Juan, Puerto Rico. · 4 Department of Medicine, Division of Rheumatology, The University of Texas-Health Science Center at Houston, Houston, USA. · 5 Department of Epidemiology, Schools of Medicine and Public Health, The University of Alabama at Birmingham, Birmingham, USA. · 6 Department of Medicine, Division of Clinical Immunology and Rheumatology, School of Medicine, The University of Alabama at Birmingham, Birmingham, USA. ·Lupus · Pubmed #27558795.

ABSTRACT: Objective The objective of this study was to determine the association of disease expression patterns with demographic and clinical characteristics in SLE. Methods Patients from a multi-ethnic SLE cohort were included. Disease expression patterns were defined as acute SLE and insidious SLE; this group was divided into those who accrued three ACR criteria and then accrued the fourth (insidious pattern A) and those who have one or two and then accrued four criteria (insidious pattern B). Disease activity was ascertained with the SLAM-R and disease damage with SLICC/ACR damage index. Variables were compared using analysis of variance for numeric variables and χ

6 Article Efficacy of immunosuppressive treatment in a systemic lupus erythematosus patient presenting with inclusion body myositis. 2016

Varela-Rosario, Noemí / Pérez-Berenguer, Juan L / Vilá, Luis M. ·Department of Medicine, Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. · Department of Pathology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. ·BMJ Case Rep · Pubmed #27048400.

ABSTRACT: Inclusion body myositis (IBM) is an inflammatory myopathy that is generally unresponsive to immunosuppressive drugs. The coexistence of IBM with other autoimmune connective tissue diseases is rare. We present a case of a 76-year-old woman with systemic lupus erythematosus (SLE) who developed proximal muscle weakness of lower extremities and mild elevation of serum creatine kinase (CK) at 495 U/L. Muscle biopsy showed changes of endomysial inflammation and rimmed vacuoles consistent with IBM. She was treated with prednisone 40 mg daily and methotrexate 12.5 mg weekly. One month later, her physical examination showed minimal proximal weakness of lower extremities. CK levels decreased to 44 U/L. Prednisone dose was gradually decreased to 5.0 mg daily. She remained stable with normal CK levels during a follow-up period of 10 months. This case, together with other reports, suggests that IBM in the setting of SLE represents a different subtype that can benefit from immunosuppressive treatment.

7 Article Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production. 2016

Deng, Yun / Zhao, Jian / Sakurai, Daisuke / Sestak, Andrea L / Osadchiy, Vadim / Langefeld, Carl D / Kaufman, Kenneth M / Kelly, Jennifer A / James, Judith A / Petri, Michelle A / Bae, Sang-Cheol / Alarcón-Riquelme, Marta E / Alarcón, Graciela S / Anaya, Juan-Manuel / Criswell, Lindsey A / Freedman, Barry I / Kamen, Diane L / Gilkeson, Gary S / Jacob, Chaim O / Merrill, Joan T / Gaffney, Patrick M / Sivils, Kathy Moser / Niewold, Timothy B / Ramsey-Goldman, Rosalind / Reveille, John D / Scofield, R Hal / Stevens, Anne M / Boackle, Susan A / Vilá, Luis M / Sohn, I I Woong / Lee, Seung / Chang, Deh-Ming / Song, Yeong Wook / Vyse, Timothy J / Harley, John B / Brown, Elizabeth E / Edberg, Jeffrey C / Kimberly, Robert P / Cantor, Rita M / Hahn, Bevra H / Grossman, Jennifer M / Tsao, Betty P. ·Division of Rheumatology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. · Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. · Department of Biostatistical Sciences, Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. · Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. · Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Pfizer-Universidad de Granada-Junta de Andalucía Center for Genomics and Oncological Research, Granada, Spain. · Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Center for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, Colombia. · Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, California, USA. · Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. · Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA. · Department of Medicine, University of Southern California, Los Angeles, California, USA. · Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. · Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA. · Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. · Department of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA US Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA. · Division of Rheumatology, Department of Pediatrics, University of Washington, Seattle, Washington, USA Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA. · Division of Rheumatology, University of Colorado School of Medicine, Aurora, Colorado, USA US Department of Veterans Affairs Medical Center, Denver, Colorado, USA. · Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. · Taipei Veterans General Hospital, Taipei City, Taiwan. · Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Medical Research Center, Seoul National University, Seoul, Korea. · Division of Genetics and Molecular Medicine and Immunology, King's College London, London, UK. · Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Department of Human Genetics, University of California Los Angeles, Los Angeles, California, USA. ·Ann Rheum Dis · Pubmed #26783109.

ABSTRACT: OBJECTIVES: Following up the systemic lupus erythematosus (SLE) genome-wide association studies (GWAS) identification of NMNAT2 at rs2022013, we fine-mapped its 150 kb flanking regions containing NMNAT2 and SMG7 in a 15 292 case-control multi-ancestry population and tested functions of identified variants. METHODS: We performed genotyping using custom array, imputation by IMPUTE 2.1.2 and allele specific functions using quantitative real-time PCR and luciferase reporter transfections. SLE peripheral blood mononuclear cells (PBMCs) were cultured with small interfering RNAs to measure antinuclear antibody (ANA) and cyto/chemokine levels in supernatants using ELISA. RESULTS: We confirmed association at NMNAT2 in European American (EA) and Amerindian/Hispanic ancestries, and identified independent signal at SMG7 tagged by rs2702178 in EA only (p=2.4×10 CONCLUSION: We confirmed NMNAT2 and identified independent SMG7 association with SLE. The inverse relationship between levels of the risk allele-associated SMG7 mRNAs and ANA suggested the novel contribution of mRNA surveillance pathway to SLE pathogenesis.

8 Article Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA. 2016

Zhao, Jian / Giles, Brendan M / Taylor, Rhonda L / Yette, Gabriel A / Lough, Kara M / Ng, Han Leng / Abraham, Lawrence J / Wu, Hui / Kelly, Jennifer A / Glenn, Stuart B / Adler, Adam J / Williams, Adrienne H / Comeau, Mary E / Ziegler, Julie T / Marion, Miranda / Alarcón-Riquelme, Marta E / Anonymous1290805 / Alarcón, Graciela S / Anaya, Juan-Manuel / Bae, Sang-Cheol / Kim, Dam / Lee, Hye-Soon / Criswell, Lindsey A / Freedman, Barry I / Gilkeson, Gary S / Guthridge, Joel M / Jacob, Chaim O / James, Judith A / Kamen, Diane L / Merrill, Joan T / Sivils, Kathy Moser / Niewold, Timothy B / Petri, Michelle A / Ramsey-Goldman, Rosalind / Reveille, John D / Scofield, R Hal / Stevens, Anne M / Vilá, Luis M / Vyse, Timothy J / Kaufman, Kenneth M / Harley, John B / Langefeld, Carl D / Gaffney, Patrick M / Brown, Elizabeth E / Edberg, Jeffrey C / Kimberly, Robert P / Ulgiati, Daniela / Tsao, Betty P / Boackle, Susan A. ·Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA. · Division of Rheumatology, University of Colorado School of Medicine, Aurora, Colorado, USA. · School of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, Western Australia, Australia. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. · Department of Biostatistical Sciences and Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Pfizer-Universidad de Granada-Junta de Andalucía Center for Genomics and Oncological Research, Granada, Spain. · Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Center for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, Colombia. · Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea. · Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, California, USA. · Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA. · Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina, USA. · Department of Medicine, University of Southern California, Los Angeles, California, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. · Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. · Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA. · Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. · Department of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA US Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma, USA. · Division of Rheumatology, Department of Pediatrics, University of Washington, Seattle, Washington, USA Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA. · Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. · Division of Genetics and Molecular Medicine and Immunology, King's College London, London, UK. · Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA US Department of Veterans Affairs Medical Center, Cincinnati, Ohio, USA. · Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. · Division of Rheumatology, University of Colorado School of Medicine, Aurora, Colorado, USA Denver Veterans Affairs Medical Center, Denver, Colorado, USA. ·Ann Rheum Dis · Pubmed #25180293.

ABSTRACT: OBJECTIVES: Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association. METHODS: Genotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR. RESULTS: The strongest association signal was detected at rs1876453 in intron 1 of CR2 (pmeta=4.2×10(-4), OR 0.85), specifically when subjects were stratified based on the presence of dsDNA autoantibodies (case-control pmeta=7.6×10(-7), OR 0.71; case-only pmeta=1.9×10(-4), OR 0.75). Although allele-specific effects on B cell CR2 mRNA or protein levels were not identified, levels of complement receptor 1 (CR1/CD35) mRNA and protein were significantly higher on B cells of subjects harbouring the minor allele (p=0.0248 and p=0.0006, respectively). The minor allele altered the formation of several DNA protein complexes by EMSA, including one containing CCCTC-binding factor (CTCF), an effect that was confirmed by ChIP-PCR. CONCLUSIONS: These data suggest that rs1876453 in CR2 has long-range effects on gene regulation that decrease susceptibility to lupus. Since the minor allele at rs1876453 is preferentially associated with reduced risk of the highly specific dsDNA autoantibodies that are present in preclinical, active and severe lupus, understanding its mechanisms will have important therapeutic implications.

9 Article Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus. 2015

Zhao, Jian / Wu, Hui / Langefeld, Carl D / Kaufman, Kenneth M / Kelly, Jennifer A / Bae, Sang-Cheol / Anonymous740843 / Alarcón, Graciela S / Anaya, Juan-Manuel / Criswell, Lindsey A / Freedman, Barry I / Kamen, Diane L / Gilkeson, Gary S / Jacob, Chaim O / James, Judith A / Merrill, Joan T / Gaffney, Patrick M / Sivils, Kathy Moser / Niewold, Timothy B / Petri, Michelle A / Song, Seung Taek / Jeong, Hye-Jin / Ramsey-Goldman, Rosalind / Reveille, John D / Scofield, R Hal / Stevens, Anne M / Boackle, Susan A / Vilá, Luis M / Chang, Deh-Ming / Song, Yeong Wook / Vyse, Timothy J / Harley, John B / Brown, Elizabeth E / Edberg, Jeffrey C / Kimberly, Robert P / Hahn, Bevra H / Grossman, Jennifer M / Tsao, Betty P / La Cava, Antonio. ·Department of Medicine, University of California Los Angeles, Los Angeles, CA, United States. · Department of Biostatistical Sciences and Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, NC, United States. · Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; US Department of Veterans Affairs Medical Center, Cincinnati, OH, United States. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States. · Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea. · Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States. · Center for Autoimmune Diseases Research, Universidad del Rosario, Bogotá, Colombia. · Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, CA, United States. · Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States. · Medical University of South Carolina, Charleston, SC, United States. · Department of Medicine, University of Southern California, Los Angeles, CA, United States. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States. · Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States. · Department of Immunology, Mayo Clinic, Rochester, MN, United States. · Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States. · Northwestern University Feinberg School of Medicine, Chicago, IL, United States. · Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, TX, United States. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; US Department of Veterans Affairs Medical Center, Oklahoma City, OK, United States. · Department of Pediatrics, University of Washington, Seattle, WA, United States; Center for Immunity and Immunotherapies, Seattle Children's Research Institute Seattle, WA, United States. · University of Colorado School of Medicine, Aurora, CO, United States; US Department of Veterans Affairs Medical Center, Denver, CO, United States. · Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. · National Defense Medical Center, Taipei City, Taiwan. · Seoul National University, Seoul, South Korea. · King's College London, London, UK. · Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, United States. · Department of Medicine, University of California Los Angeles, Los Angeles, CA, United States. Electronic address: btsao@mednet.ucla.edu. · Department of Medicine, University of California Los Angeles, Los Angeles, CA, United States. Electronic address: alacava@mednet.ucla.edu. ·Clin Immunol · Pubmed #26385092.

ABSTRACT: Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE.

10 Article Efficacy of intravenous immunoglobulins in a patient with systemic lupus erythematosus presenting with Stevens-Johnson syndrome. 2015

Vázquez-Sanabria, Irma L / Mercado-Seda, Rogelio / Varela-Rosario, Noemí / Vilá, Luis M. ·Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. · Department of Dermatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. ·BMJ Case Rep · Pubmed #26202316.

ABSTRACT: -- No abstract --

11 Article Clinical associations of anti-Smith antibodies in PROFILE: a multi-ethnic lupus cohort. 2015

Arroyo-Ávila, Mariangelí / Santiago-Casas, Yesenia / McGwin, Gerald / Cantor, Ryan S / Petri, Michelle / Ramsey-Goldman, Rosalind / Reveille, John D / Kimberly, Robert P / Alarcón, Graciela S / Vilá, Luis M / Brown, Elizabeth E. ·Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, PO Box 365067, San Juan, PR, 00936-5067, USA. ·Clin Rheumatol · Pubmed #25896533.

ABSTRACT: The aim of this study was to determine the association of anti-Sm antibodies with clinical manifestations, comorbidities, and disease damage in a large multi-ethnic SLE cohort. SLE patients (per American College of Rheumatology criteria), age ≥16 years, disease duration ≤10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal US cohort were studied. Socioeconomic-demographic features, cumulative clinical manifestations, comorbidities, and disease damage (as per the Systemic Lupus International Collaborating Clinics Damage Index [SDI]) were determined. The association of anti-Sm antibodies with clinical features was examined using multivariable logistic regression analyses adjusting for age, gender, ethnicity, disease duration, level of education, health insurance, and smoking. A total of 2322 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.4 (12.8) years and the mean (SD) disease duration was 9.0 (7.9) years; 2127 (91.6%) were women. Anti-Sm antibodies were present in 579 (24.9%) patients. In the multivariable analysis, anti-Sm antibodies were significantly associated with serositis, renal involvement, psychosis, vasculitis, Raynaud's phenomenon, hemolytic anemia, leukopenia, lymphopenia, and arterial hypertension. No significant association was found for damage accrual. In this cohort of SLE patients, anti-Sm antibodies were associated with several clinical features including serious manifestations such as renal, neurologic, and hematologic disorders as well as vasculitis.

12 Article Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression. 2015

Lu, Xiaoming / Zoller, Erin E / Weirauch, Matthew T / Wu, Zhiguo / Namjou, Bahram / Williams, Adrienne H / Ziegler, Julie T / Comeau, Mary E / Marion, Miranda C / Glenn, Stuart B / Adler, Adam / Shen, Nan / Nath, Swapan K / Stevens, Anne M / Freedman, Barry I / Tsao, Betty P / Jacob, Chaim O / Kamen, Diane L / Brown, Elizabeth E / Gilkeson, Gary S / Alarcón, Graciela S / Reveille, John D / Anaya, Juan-Manuel / James, Judith A / Sivils, Kathy L / Criswell, Lindsey A / Vilá, Luis M / Alarcón-Riquelme, Marta E / Petri, Michelle / Scofield, R Hal / Kimberly, Robert P / Ramsey-Goldman, Rosalind / Joo, Young Bin / Choi, Jeongim / Bae, Sang-Cheol / Boackle, Susan A / Graham, Deborah Cunninghame / Vyse, Timothy J / Guthridge, Joel M / Gaffney, Patrick M / Langefeld, Carl D / Kelly, Jennifer A / Greis, Kenneth D / Kaufman, Kenneth M / Harley, John B / Kottyan, Leah C. ·Immunology Graduate Program, College of Medicine, University of Cincinnati, Cincinnati, OH 45229, USA; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. · Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. · Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. · Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. · Center for Public Health Genomics and Department of Biostatistical Sciences, Wake Forest School of Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. · Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Joint Molecular Rheumatology Laboratory, Institute of Health Sciences and Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine in collaboration with Shanghai Institutes for Biological Sciences and Chinese Academy of Sciences, Shanghai 200031, PRC. · Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA 98101, USA; Division of Rheumatology, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA. · Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA. · Division of Rheumatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA. · Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA. · Division of Rheumatology, Medical University of South Carolina, Charleston, SC 29425, USA. · Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. · Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. · Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. · Center for Autoimmune Diseases Research, Universidad del Rosario, 110010 Bogota, Colombia. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. · Rosalind Russell / Ephraim P. Engleman Rheumatology Research Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94117, USA. · Division of Rheumatology, Department of Medicine, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Center for Genomics and Oncological Research, Pfizer-University of Granada-Junta de Andalucia, Granada 18016, Spain. · Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Oklahoma City Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA. · Division of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. · Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-792, Korea. · Division of Rheumatology, School of Medicine, University of Colorado, Aurora, CO 80045, USA. · Divisions of Genetics and Molecular Medicine and Immunology, King's College London, Strand, London WC2R 2LS, UK. · Cancer Biology, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA. · Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA. · Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA. Electronic address: leah.kottyan@cchmc.org. ·Am J Hum Genet · Pubmed #25865496.

ABSTRACT: Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been associated with systemic lupus erythematosus (SLE), or lupus, in independent cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a critical driver of immune cell function and differentiation, and mice deficient in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of 14,551 subjects from multi-ancestral cohorts by starting with genotyped variants and imputing to all common variants spanning ETS1. By constructing genetic models via frequentist and Bayesian association methods, we identified 16 variants that are statistically likely to be causal. We functionally assessed each of these variants on the basis of their likelihood of affecting transcription factor binding, miRNA binding, or chromatin state. Of the four variants that we experimentally examined, only rs6590330 differentially binds lysate from B cells. Using mass spectrometry, we found more binding of the transcription factor signal transducer and activator of transcription 1 (STAT1) to DNA near the risk allele of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed that the risk allele increased binding to the active form of STAT1. Analysis with expression quantitative trait loci indicated that the risk allele of rs6590330 is associated with decreased ETS1 expression in Han Chinese, but not other ancestral cohorts. We propose a model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1.

13 Article Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study. 2015

Martins, M / Williams, A H / Comeau, M / Marion, M / Ziegler, J T / Freedman, B I / Merrill, J T / Glenn, S B / Kelly, J A / Sivils, K M / James, J A / Guthridge, J M / Alarcón-Riquelme, M E / Bae, S-C / Kim, J-H / Kim, D / Anaya, J-M / Boackle, S A / Criswell, L A / Kimberly, R P / Alarcón, G S / Brown, E E / Vilá, L M / Petri, M A / Ramsey-Goldman, R / Niewold, T B / Tsao, B P / Gilkeson, G S / Kamen, D L / Jacob, C O / Stevens, A M / Gaffney, P M / Harley, J B / Langefeld, C D / Fesel, C. ·1] Instituto de Medicina Molecular, Lisboa, Portugal [2] Instituto Gulbenkian de Ciência, Oeiras, Portugal. · Center for Public Health Genomics and Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA. · Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA. · Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. · Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. · 1] Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA [2] Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. · 1] Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA [2] Centro de Genómica e Investigaciones Oncológicas (GENYO), Pfizer-Universidad de Granada-Junta de Andalucía, Granada, Spain. · Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea. · Center for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogota, Colombia. · Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA. · Rosalind Russell Medical Research Center for Arthritis, Department of Medicine, University of California, San Francisco, CA, USA. · Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. · Departments of Medicine and Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. · Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. · Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. · Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. · Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, MN, USA. · Division of Rheumatology, University of California Los Angeles, Los Angeles, CA, USA. · Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. · Department of Medicine, University of Southern California, Los Angeles, CA, USA. · Center for Immunity and Immunotherapies, Seattle Children's Research Institute Arthritis Foundation, Seattle, WA, USA. · 1] Division of Rheumatology and the Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA [2] US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA. · Instituto Gulbenkian de Ciência, Oeiras, Portugal. ·Genes Immun · Pubmed #25569266.

ABSTRACT: A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.

14 Article The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. 2015

Kottyan, Leah C / Zoller, Erin E / Bene, Jessica / Lu, Xiaoming / Kelly, Jennifer A / Rupert, Andrew M / Lessard, Christopher J / Vaughn, Samuel E / Marion, Miranda / Weirauch, Matthew T / Namjou, Bahram / Adler, Adam / Rasmussen, Astrid / Glenn, Stuart / Montgomery, Courtney G / Hirschfield, Gideon M / Xie, Gang / Coltescu, Catalina / Amos, Chris / Li, He / Ice, John A / Nath, Swapan K / Mariette, Xavier / Bowman, Simon / Anonymous6770805 / Rischmueller, Maureen / Lester, Sue / Brun, Johan G / Gøransson, Lasse G / Harboe, Erna / Omdal, Roald / Cunninghame-Graham, Deborah S / Vyse, Tim / Miceli-Richard, Corinne / Brennan, Michael T / Lessard, James A / Wahren-Herlenius, Marie / Kvarnström, Marika / Illei, Gabor G / Witte, Torsten / Jonsson, Roland / Eriksson, Per / Nordmark, Gunnel / Ng, Wan-Fai / Anonymous6780805 / Anaya, Juan-Manuel / Rhodus, Nelson L / Segal, Barbara M / Merrill, Joan T / James, Judith A / Guthridge, Joel M / Scofield, R Hal / Alarcon-Riquelme, Marta / Bae, Sang-Cheol / Boackle, Susan A / Criswell, Lindsey A / Gilkeson, Gary / Kamen, Diane L / Jacob, Chaim O / Kimberly, Robert / Brown, Elizabeth / Edberg, Jeffrey / Alarcón, Graciela S / Reveille, John D / Vilá, Luis M / Petri, Michelle / Ramsey-Goldman, Rosalind / Freedman, Barry I / Niewold, Timothy / Stevens, Anne M / Tsao, Betty P / Ying, Jun / Mayes, Maureen D / Gorlova, Olga Y / Wakeland, Ward / Radstake, Timothy / Martin, Ezequiel / Martin, Javier / Siminovitch, Katherine / Moser Sivils, Kathy L / Gaffney, Patrick M / Langefeld, Carl D / Harley, John B / Kaufman, Kenneth M. ·Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA leah.kottyan@cchmc.org. · Division of Rheumatology, Center for Autoimmune Genomics and Etiology and leah.kottyan@cchmc.org. · Division of Rheumatology, Center for Autoimmune Genomics and Etiology and. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA. · Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Department of Pathology and. · Department of Biostatistical Sciences and Center for Public Health Genomics and. · Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. · NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK. · Mount Sinai Hospital Samuel Lunenfeld Research Institute, Toronto, ON, Canada. · Liver Centre, Toronto Western Hospital, Toronto, ON, Canada. · Department of Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA. · Department of Rheumatology, Hôpitaux Universitaires Paris-Sud, INSERM U1012, Le Kremlin Bicêtre, France. · Rheumatology Department, University Hospital Birmingham, Birmingham, UK. · The Queen Elizabeth Hospital, Adelaide, Australia. · The Queen Elizabeth Hospital, Adelaide, Australia The University of Adelaide, Adelaide, Australia. · Institute of Internal Medicine, University of Bergen, Bergen, Norway Department of Rheumatology, Haukeland University Hospital, Bergen, Norway. · Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway. · Department of Medical and Molecular Genetics, King's College London, London, UK. · Department of Oral Medicine, Carolinas Medical Center, Charlotte, NC, USA. · Valley Bone and Joint Clinic, Grand Forks, ND, USA. · Department of Medicine, Karolinska Institute, Stockholm, Sweden. · National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA. · Hannover Medical School, Hanover, Germany. · Department of Rheumatology, Haukeland University Hospital, Bergen, Norway Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway. · Department of Rheumatology, Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. · Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden. · Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK. · Center for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogotá, Colombia. · Department of Oral Surgery, University of Minnesota School of Dentistry, Minneapolis, MN, USA. · Division of Rheumatology, University of Minnesota Medical School, Minneapolis, MN, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA Division of Veterans Affairs Medical Center, Oklahoma City, OK, USA Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. · Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA de Genómica e Investigación Oncológica (GENYO), Pfizer-Universidad de Granada-Junta de Andalucia, Granada, Spain. · Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea. · Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA. · Division of Rheumatology, Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, CA, USA. · Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, USA. · Divison of Gastrointestinal and Liver Diseases, Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. · Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. · Division of Rheumatology and Clinical Immunogenetics, The Univeristy of Texas Health Science Center at Houston, Houston, TX, USA. · University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico, USA. · Division of Rheumatology, Johns Hopkins, Baltimore, MD, USA. · Division of Rheumatology, Northwestern University, Chicago, IL, USA. · Wake Forest School of Medicine, Winston-Salem, NC, USA. · Division of Rheumatology and Immunology, Mayo Clinic, Rochester, MN, USA. · University of Washington and Seattle Children's Hospital, Seattle, WA, USA. · David Geffen School of Medicine, University of California, Los Angeles, CA, USA. · MD Anderson Cancer Center, University of Texas, Houston, TX, USA. · University of Texas Southwestern Medical School, Dallas, TX, USA. · Department of Rheumatology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands. · Instituto de Parasitología y Biomedicina López Neyra Avda, Granada, Spain and. · Mount Sinai Hospital Samuel Lunenfeld Research Institute, Toronto, ON, Canada Department of Medicine, University of Toronto, Toronto, ON, Canada. · Division of Rheumatology, Center for Autoimmune Genomics and Etiology and US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA. ·Hum Mol Genet · Pubmed #25205108.

ABSTRACT: Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.

15 Article Mitochondrial DNA damage is associated with damage accrual and disease duration in patients with systemic lupus erythematosus. 2014

López-López, L / Nieves-Plaza, M / Castro, M del R / Font, Y M / Torres-Ramos, C A / Vilá, L M / Ayala-Peña, S. ·Department of Medicine (Division of Rheumatology), University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. · Puerto Rico Clinical and Translational Research Consortium, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico School of Medicine, Institute for Clinical Research Education, University of Pittsburgh, Pittsburgh, Pennsylvania. · Department of Pharmacology and Toxicology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. · Department of Physiology and Biophysics, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. · Department of Pharmacology and Toxicology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico sylvette.ayala@upr.edu. ·Lupus · Pubmed #24899636.

ABSTRACT: OBJECTIVE: To determine the extent of mitochondrial DNA (mtDNA) damage in systemic lupus erythematosus (SLE) patients compared to healthy subjects and to determine the factors associated with mtDNA damage among SLE patients. METHODS: A cross-sectional study was performed in 86 SLE patients (per American College of Rheumatology classification criteria) and 86 healthy individuals matched for age and gender. Peripheral blood mononuclear cells (PBMCs) were collected from subjects to assess the relative amounts of mtDNA damage. Quantitative polymerase chain reaction assay was used to measure the frequency of mtDNA lesions and mtDNA abundance. Socioeconomic-demographic features, clinical manifestations, pharmacologic treatment, disease activity, and damage accrual were determined. Statistical analyses were performed using t test, pairwise correlation, and Pearson's chi-square test (or Fisher's exact test) as appropriate. RESULTS: Among SLE patients, 93.0% were women. The mean (SD) age was 38.0 (10.4) years and the mean (SD) disease duration was 8.7 (7.5) years. SLE patients exhibited increased levels of mtDNA damage as shown by higher levels of mtDNA lesions and decreased mtDNA abundance as compared to healthy individuals. There was a negative correlation between disease damage and mtDNA abundance and a positive correlation between mtDNA lesions and disease duration. No association was found between disease activity and mtDNA damage. CONCLUSION: PBMCs from SLE patients exhibited more mtDNA damage compared to healthy subjects. Higher levels of mtDNA damage were observed among SLE patients with major organ involvement and damage accrual. These results suggest that mtDNA damage have a potential role in the pathogenesis of SLE.

16 Article Two functional lupus-associated BLK promoter variants control cell-type- and developmental-stage-specific transcription. 2014

Guthridge, Joel M / Lu, Rufei / Sun, Harry / Sun, Celi / Wiley, Graham B / Dominguez, Nicolas / Macwana, Susan R / Lessard, Christopher J / Kim-Howard, Xana / Cobb, Beth L / Kaufman, Kenneth M / Kelly, Jennifer A / Langefeld, Carl D / Adler, Adam J / Harley, Isaac T W / Merrill, Joan T / Gilkeson, Gary S / Kamen, Diane L / Niewold, Timothy B / Brown, Elizabeth E / Edberg, Jeffery C / Petri, Michelle A / Ramsey-Goldman, Rosalind / Reveille, John D / Vilá, Luis M / Kimberly, Robert P / Freedman, Barry I / Stevens, Anne M / Boackle, Susan A / Criswell, Lindsey A / Vyse, Tim J / Behrens, Timothy W / Jacob, Chaim O / Alarcón-Riquelme, Marta E / Sivils, Kathy L / Choi, Jiyoung / Joo, Young Bin / Bang, So-Young / Lee, Hye-Soon / Bae, Sang-Cheol / Shen, Nan / Qian, Xiaoxia / Tsao, Betty P / Scofield, R Hal / Harley, John B / Webb, Carol F / Wakeland, Edward K / James, Judith A / Nath, Swapan K / Graham, Robert R / Gaffney, Patrick M. ·Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: guthridgej@omrf.org. · Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. · Immune and Tissue Growth and Repair and Human Genetics Department, Genentech, South San Francisco, CA 94080, USA. · Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. · Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. · Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA. · Department of Biostatistical Sciences, Wake Forest University, Winston-Salem, NC 27106, USA. · Division of Molecular Immunology and Graduate Program in Immunobiology, Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229, USA. · Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. · Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, SC 29425, USA. · Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, MN 55902, USA. · Department of Epidemiology, University of Alabama-Birmingham, Birmingham, AL 35294, USA; Department of Medicine, University of Alabama-Birmingham, Birmingham, AL 35294, USA. · Division of Clinical Immunology and Rheumatology, University of Alabama-Birmingham School of Medicine, Birmingham, AL 35294, USA. · Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. · Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. · Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, TX.77030, USA. · Department of Medicine, Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan 00921, Puerto Rico. · Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27106, USA. · Division of Rheumatology, Department of Pediatrics, University of Washington Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA 98101, USA. · Division of Rheumatology, University of Colorado Denver, Aurora, CO 80045, USA. · Rosalind Russell Medical Research Center for Arthritis, University of California San Francisco, San Francisco, CA 94143, USA. · Division of Medicine, Imperial College of London, London SW7 2AZ, UK. · Department of Medicine, University of Southern California, Los Angeles, CA 90089, USA. · Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Centro de Genómica e Investigaciones Oncológicas (GENYO). Pfizer-Universidad de Granada-Junta de Andalucía, Granada 18016, Spain. · Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 133-791, Korea. · Molecular Rheumatology Laboratory, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. · Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA. · Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73105, USA; United States Department of Veterans Affairs Medical Center, Oklahoma City, OK 73105, USA. · Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Cell Biology and Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. · Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA. · Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73105, USA. ·Am J Hum Genet · Pubmed #24702955.

ABSTRACT: Efforts to identify lupus-associated causal variants in the FAM167A/BLK locus on 8p21 are hampered by highly associated noncausal variants. In this report, we used a trans-population mapping and sequencing strategy to identify a common variant (rs922483) in the proximal BLK promoter and a tri-allelic variant (rs1382568) in the upstream alternative BLK promoter as putative causal variants for association with systemic lupus erythematosus. The risk allele (T) at rs922483 reduced proximal promoter activity and modulated alternative promoter usage. Allelic differences at rs1382568 resulted in altered promoter activity in B progenitor cell lines. Thus, our results demonstrated that both lupus-associated functional variants contribute to the autoimmune disease association by modulating transcription of BLK in B cells and thus potentially altering immune responses.

17 Article Lymphocyte sensitivity assay as a marker for glucocorticoid resistance in lupus: report of two sisters with systemic lupus erythematosus. 2014

Fajardo-Hermosillo, L D / Rodríguez-Navedo, Y / Nadal, A J / Vilá, L M. ·Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, Puerto Rico. ·Lupus · Pubmed #24285097.

ABSTRACT: Glucocorticoid sensitivity can be measured in vitro using the lymphocyte sensitivity assay (LSA). In this test, dexamethasone is used to inhibit the proliferation of peripheral blood mononuclear cells (PBMC) in response to mitogens. If the proliferation of PBMC is suppressed the subjects are considered to be GC sensitive; if not, they are considered to be resistant. The LSA has been used to test GC sensitivity in some inflammatory diseases but its clinical value in systemic lupus erythematosus (SLE) has not been determined. Herein, we present the results of the LSA from two sisters with SLE who had different disease outcomes. Patient 1 presented with higher disease activity and damage accrual, and poorer response to corticosteroids than patient 2. In the LSA, patient 1 had a lower dexamethasone suppression of mitogen-stimulated PBMC than patient 2 and one control subject. The LSA could be helpful in identifying patients with GC resistance, thus allowing the consideration of alternative immunosuppressive drugs.

18 Article Pulmonary hemorrhage in a patient initially presenting with discoid lupus. 2013

Vilá-Rivera, Karina / Jiménez-Encarnación, Esther / Vilá, Salvador. ·Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. ·P R Health Sci J · Pubmed #24397219.

ABSTRACT: As a cutaneous variant of lupus erythematosus, discoid lupus erythematosus (DLE) is thought to have a good prognosis; however, the involvement of internal organs with a transition to systemic disease may occur. The progression from DLE to systemic lupus erythematosus has been reported in up to 28% of patients. This progression to systemic disease has been associated with a benign course. Herein, we report the case of a 31-year-old woman with a 10-year history of discoid lupus, now presenting with dyspnea and pleuritic chest pain of 1 month's duration. A significant drop in hemoglobin and hematocrit levels was observed in association with leukopenia, lymphopenia, a positive ANA, and hypocomplementemia. Chest radiography and computed tomography revealed bilateral infiltrates. An open lung biopsy confirmed the presence of intra-alveolar hemorrhage. Based on the results of the tests and analyses detailed herein, a diagnosis of pulmonary hemorrhage secondary to systemic lupus erythematosus was made. To our knowledge, pulmonary hemorrhage as the initial manifestation of the systemic involvement of discoid lupus has not been reported before.

19 Article An unexpected side-effect of a commonly used drug. 2013

Fernández González, Francisco / Miranda, Samayra / Santiago Casiano, Mónica / Nieves, José / Adorno, Edgardo / Fernández González, Ricardo. ·Internal Medicine Department San Juan City Hospital, San Juan Puerto Rico. frank1298@hotmail.com ·Bol Asoc Med P R · Pubmed #24282922.

ABSTRACT: We report a case of a 68 year-old-female patient with clinical features of drug-induced lupus erythematosus after five years of treatment with amiodarone. She presented generalized skin rash, arthralgia on upper and lower extremities, associated with difficulty to walk. Remarkable laboratory results revealed a positive antinuclear antibody test and a skin rash biopsy showing a superficial and deep perivascular infiltrate of lymphocytes, histiocytes, and eosinophils. Once the etiology of the patient's symptoms was identified, the culprit drug was removed and she had a complete remission of all signs and symptoms. Early diagnose should be recognized for prompt intervention and avoid further complications associated with this rare side-effect.

20 Article Efficacy of low-dose intravenous cyclophosphamide in systemic lupus erythematosus presenting with Guillain-Barre syndrome-like acute axonal neuropathies: report of two cases. 2013

Santiago-Casas, Y / Peredo, R A / Vilá, L M. ·Department of Medicine, Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, Puerto Rico. ·Lupus · Pubmed #23439473.

ABSTRACT: There are few cases of Guillain-Barré syndrome (GBS), particularly of atypical variants, occurring in association with systemic lupus erythematous (SLE). Reports addressing a specific therapy thus remain almost anecdotal. It is therefore challenging to determine the treatment that is best suited for this subset of patients, especially if initial conventional therapy for GBS fails. We present two cases of GBS-like acute axonal neuropathies, one with acute motor axonal neuropathy (AMAN), and another with acute motor sensory axonal neuropathy (AMSAN), presenting early in the course of SLE. The first case failed to respond to therapy with intravenous immunoglobulins (IVIG) and plasmapheresis, but achieved a favorable outcome when high-dose glucocorticoids along with low-dose intravenous (IV) cyclophosphamide pulses were given. The second case responded favorably to high-dose glucocorticoids, IVIG, and low-dose IV cyclophosphamide pulses. Both patients have remained in clinical remission and without neurologic sequelae after 10 and three years of follow-up, respectively.

21 Article Renal biopsies in Puerto Rico patients with lupus nephritis. 2012

Rodríguez, Vanessa E / Rodríguez, Noelia / Mayor, Angel / Negrón, Diana. ·Division of Rheumatology, Allergy and Immunology, Department of Medicine, UPR School of Medicine and Puerto Rico Medical Science Campus, San Juan, Puerto Rico 00936-5067. vanessa.rodriguez13@upr.edu ·Bol Asoc Med P R · Pubmed #23882974.

ABSTRACT: The purpose of was to evaluate the renal pathology findings as described by the World Health Organization classification for systemic lupus erythematosus (SLE) in a group of Puerto Rico patients with lupus nephritis and determine the association with clinical and laboratory findings. The medical records from patients seen at the Lu pus Clinic from 1985 to 2005 were reviewed and patients with a performed renal biopsy included. All patients fulfilled the American ColIege of Rheumatology criteria for SLE. Data gathered from the medical records included demographics, cumulative clinical manifestations and serologic tests at the time of the renal biopsy. There were 139 patients with lupus nephntis (LN) and 71 patients (51%) had a renal biopsy done. From these 86% were females and their mean age at LN diagnosis was 25 years. The mean time between diagnosis of LN and renal biopsy was 1.5 years. The most frequent renal pathology was membranous glomewlonephritis (GN) class V (37%) followed by mesangial GN class II (23%). All groups were similar in clinical manifestations and laboratory parameters. The majority of Puerto Rico patients with LN had membranous GN class V. This data is different from other ethnic groups were diffuse GN type IV has been described as most prevalent.

22 Article Nitrofurantoin-induced microangiopathic haemolytic anaemia and thrombocytopaenia in a patient with systemic lupus erythematosus. 2012

López-López, Linnette / Rivera-Rodríguez, Noridza / Vilá, Luis M. ·Department of Medicine, Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. ·BMJ Case Rep · Pubmed #22977056.

ABSTRACT: Patients with systemic lupus erythematosus (SLE) may develop thrombotic thrombocytopaenic purpura (TTP) or TTP-like illness manifested by microangiopathic haemolytic anaemia (MAHA) and thrombocytopaenia. The distinction between active SLE and TTP is difficult because these entities share similar clinical features. Drug-induced TTP caused by an immune-mediated reaction have been documented for several drugs. Herein, we report a middle-aged Hispanic woman with long-standing SLE, who developed a TTP-like illness characterised by MAHA and thrombocytopaenia after exposure to nitrofurantoin. The patient responded well to plasmapheresis and immunosuppressive therapy and has remained clinically stable after 18 months of follow-up. To our knowledge, this is the first case that reports the association between nitrofurantoin and a TTP-like presentation.

23 Article Long-term membranous glomerulonephritis as the presenting manifestation of systemic lupus erythematosus in a patient with human immunodeficiency virus infection. 2012

López-López, L / González, A / Vilá, L M. ·Division of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico. ·Lupus · Pubmed #22249649.

ABSTRACT: The coexistence of human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE) is unusual, but the occurrence of SLE after HIV infection is even less common. Both conditions share similar clinical features including constitutional symptoms, facial rash, oral ulcers, alopecia, arthralgias, arthritis, seizures, cytopenias, glomerulonephritis, and antinuclear and antiphospholipid antibodies. This clinical overlap makes the diagnosis of SLE in a patient with pre-existing HIV infection difficult. Furthermore, immune complex glomerulonephritis with features resembling lupus nephritis has been described in HIV-positive patients. We present the case of a 45-year-old Hispanic woman with long-standing HIV infection who developed membranous glomerulonephritis with histological features of lupus nephritis. Five years after onset of renal disease she developed clinically evident SLE.

24 Article Outcome and predictors of kidney disease progression in Puerto Ricans with systemic lupus erythematosus initially presenting with mild renal involvement. 2011

Nieves-Plaza, Mariely / Ortiz, Ana P / Colón, Marilú / Molina, María J / Castro-Santana, Lesliane E / Rodríguez, Vanessa E / Mayor, Angel M / Vilá, Luis M. ·Department of Biostatistics and Epidemiology, Graduate School of Public Health, University of Puerto Rico Medical Sciences Campus, San Juan, PR. ·J Clin Rheumatol · Pubmed #21617555.

ABSTRACT: OBJECTIVES: The aims of this study were to determine the outcomes and predictors of renal disease progression in Puerto Ricans with systemic lupus erythematosus (SLE) initially presenting mild renal involvement. METHODS: A retrospective cohort of 61 patients with SLE (per American College of Rheumatology classification) with mild renal involvement was studied. Mild renal disease was defined as glomerular filtration rate (GFR) of 90 mL/min or higher in the presence of proteinuria (>0.25 g/d, but <3.5 g/d), hematuria, and/or urinary cellular casts. Demographic parameters, clinical manifestations, serologic markers, comorbidities, pharmacologic treatments, disease activity, and damage accrual were determined at onset of renal disease. Factors associated with renal disease progression were evaluated using recurrent event survival analysis. RESULTS: Of 61 patients, 55 (90.2%) were women. The mean (SD) age at renal onset was 29 (11.2) years, and the mean (SD) follow-up period was 5.1 (3.4) years. Thirty-eight patients had a decline in GFR. Thirty-two had a mild decline (GFR = 60-89 mL/min), 5 developed moderate to severe renal insufficiency (GFR = 15-59 mL/min), and 1 evolved to end-stage renal disease (GFR < 15 mL/min). In the Cox model, low C4 levels and proteinuria greater than 0.5 g/d were associated with an earlier decline in GFR. CONCLUSIONS: Most Puerto Rican patients with SLE initially presenting with mild renal involvement had a decrease in GFR after an average of 5 years of kidney disease, although most had a mild dysfunction. Low C4 levels and proteinuria were predictors of an earlier decline in GFR. We emphasize that awareness of these factors may contribute to early identification of individuals at risk for renal deterioration.

25 Article Cytomegalovirus as a trigger for systemic lupus erythematosus. 2010

Pérez-Mercado, Arnaldo E / Vilá-Pérez, Salvador. ·Internal Medicine Department, Dr Ramón Ruiz Arnau University Hospital, Bayamón, Puerto Rico. aeperez@gmail.com ·J Clin Rheumatol · Pubmed #20859222.

ABSTRACT: Cytomegalovirus (CMV) infections have been associated with exacerbations of systemic lupus erythematosus (SLE). Their role in triggering this disease, however, remains a subject of debate. We present a 43-year-old man with no history of systemic illness who developed persistent signs and symptoms of a CMV-associated mononucleosis-like syndrome while fulfilling diagnostic criteria for previously undiagnosed SLE. The patient was admitted with persistent fever for 3 weeks, cervical lymphadenopathy, elevated liver function tests, and leukopenia. Further laboratory studies revealed positive antinuclear antibody, anti-dsDNA, anti-Sm/RNP, rheumatoid factor, and anticardiolipin antibodies along with decreased complement levels and proteinuria of 876 mg/dL. CMV immunoglobulin M was positive in the absence of CMV immunoglobulin G, supporting acute CMV infection. Symptoms improved with intravenous administration of methylprednisolone and ganciclovir therapy. Mechanisms by which CMV may trigger autoimmunity have been proposed, and this case could support CMV infection as a potential trigger for SLE in susceptible individuals.

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