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Systemic Lupus Erythematosus: HELP
Articles by Carlos Silva Vasconcelos
Based on 34 articles published since 2008
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Between 2008 and 2019, C. Vasconcelos wrote the following 34 articles about Lupus Erythematosus, Systemic.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. 2014

van Vollenhoven, Ronald F / Mosca, Marta / Bertsias, George / Isenberg, David / Kuhn, Annegret / Lerstrøm, Kirsten / Aringer, Martin / Bootsma, Hendrika / Boumpas, Dimitrios / Bruce, Ian N / Cervera, Ricard / Clarke, Ann / Costedoat-Chalumeau, Nathalie / Czirják, László / Derksen, Ronald / Dörner, Thomas / Gordon, Caroline / Graninger, Winfried / Houssiau, Frédéric / Inanc, Murat / Jacobsen, Søren / Jayne, David / Jedryka-Goral, Anna / Levitsky, Adrian / Levy, Roger / Mariette, Xavier / Morand, Eric / Navarra, Sandra / Neumann, Irmgard / Rahman, Anisur / Rovensky, Jozef / Smolen, Josef / Vasconcelos, Carlos / Voskuyl, Alexandre / Voss, Anne / Zakharova, Helena / Zoma, Asad / Schneider, Matthias. ·Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases, Stockholm, Sweden, Karolinska Institutet, , Stockholm, Sweden. ·Ann Rheum Dis · Pubmed #24739325.

ABSTRACT: The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE.

2 Guideline Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. 2012

Bertsias, George K / Tektonidou, Maria / Amoura, Zahir / Aringer, Martin / Bajema, Ingeborg / Berden, Jo H M / Boletis, John / Cervera, Ricard / Dörner, Thomas / Doria, Andrea / Ferrario, Franco / Floege, Jürgen / Houssiau, Frederic A / Ioannidis, John P A / Isenberg, David A / Kallenberg, Cees G M / Lightstone, Liz / Marks, Stephen D / Martini, Alberto / Moroni, Gabriela / Neumann, Irmgard / Praga, Manuel / Schneider, Matthias / Starra, Argyre / Tesar, Vladimir / Vasconcelos, Carlos / van Vollenhoven, Ronald F / Zakharova, Helena / Haubitz, Marion / Gordon, Caroline / Jayne, David / Boumpas, Dimitrios T / Anonymous430733. ·Department of Medicine, Rheumatology, Clinical Immunology and Allergy, University of Crete, Iraklion, Greece. ·Ann Rheum Dis · Pubmed #22851469.

ABSTRACT: OBJECTIVES: To develop recommendations for the management of adult and paediatric lupus nephritis (LN). METHODS: The available evidence was systematically reviewed using the PubMed database. A modified Delphi method was used to compile questions, elicit expert opinions and reach consensus. RESULTS: Immunosuppressive treatment should be guided by renal biopsy, and aiming for complete renal response (proteinuria <0.5 g/24 h with normal or near-normal renal function). Hydroxychloroquine is recommended for all patients with LN. Because of a more favourable efficacy/toxicity ratio, as initial treatment for patients with class III-IV(A) or (A/C) (±V) LN according to the International Society of Nephrology/Renal Pathology Society 2003 classification, mycophenolic acid (MPA) or low-dose intravenous cyclophosphamide (CY) in combination with glucocorticoids is recommended. In patients with adverse clinical or histological features, CY can be prescribed at higher doses, while azathioprine is an alternative for milder cases. For pure class V LN with nephrotic-range proteinuria, MPA in combination with oral glucocorticoids is recommended as initial treatment. In patients improving after initial treatment, subsequent immunosuppression with MPA or azathioprine is recommended for at least 3 years; in such cases, initial treatment with MPA should be followed by MPA. For MPA or CY failures, switching to the other agent, or to rituximab, is the suggested course of action. In anticipation of pregnancy, patients should be switched to appropriate medications without reducing the intensity of treatment. There is no evidence to suggest that management of LN should differ in children versus adults. CONCLUSIONS: Recommendations for the management of LN were developed using an evidence-based approach followed by expert consensus.

3 Review Topics on vitamin D in systemic lupus erythematosus: analysis of evidence and critical literature review. 2017

Marinho, António / Taveira, Mariana / Vasconcelos, Carlos. ·UMIB, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), U.Porto, 4099-001, Porto, Portugal. antmarinho@hotmail.com. · Unidade Imunologia Clínica, Centro Hospitalar do Porto, Hospital Santo António, Porto, Portugal. antmarinho@hotmail.com. · Serviço de Medicina Interna, ULS Matosinhos, Matosinhos, Portugal. · UMIB, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), U.Porto, 4099-001, Porto, Portugal. · Unidade Imunologia Clínica, Centro Hospitalar do Porto, Hospital Santo António, Porto, Portugal. ·Immunol Res · Pubmed #28229285.

ABSTRACT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiorgan inflammation, linked to the loss of immune tolerance to self-antigens and the production of a diversity of autoantibodies. The phenotype and progression of SLE have been linked to a combination of environmental, genetic, and hormonal factors. One such environmental factor is vitamin D, a vital hormone with well-established effects on mineral metabolism, skeletal health, and effects on cardiovascular system. The purpose of this article is to make the analysis of evidence and literature review of the pleomorphic effects of Vitamin D in SLE. The article is structured in topics of interest based in the authors' opinion and summarizes the evidence of studies and trials of vitamin D in SLE.

4 Review A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). 2017

van Vollenhoven, Ronald / Voskuyl, Alexandre / Bertsias, George / Aranow, Cynthia / Aringer, Martin / Arnaud, Laurent / Askanase, Anca / Balážová, Petra / Bonfa, Eloisa / Bootsma, Hendrika / Boumpas, Dimitrios / Bruce, Ian / Cervera, Ricard / Clarke, Ann / Coney, Cindy / Costedoat-Chalumeau, Nathalie / Czirják, László / Derksen, Ronald / Doria, Andrea / Dörner, Thomas / Fischer-Betz, Rebecca / Fritsch-Stork, Ruth / Gordon, Caroline / Graninger, Winfried / Györi, Noémi / Houssiau, Frédéric / Isenberg, David / Jacobsen, Soren / Jayne, David / Kuhn, Annegret / Le Guern, Veronique / Lerstrøm, Kirsten / Levy, Roger / Machado-Ribeiro, Francinne / Mariette, Xavier / Missaykeh, Jamil / Morand, Eric / Mosca, Marta / Inanc, Murat / Navarra, Sandra / Neumann, Irmgard / Olesinska, Marzena / Petri, Michelle / Rahman, Anisur / Rekvig, Ole Petter / Rovensky, Jozef / Shoenfeld, Yehuda / Smolen, Josef / Tincani, Angela / Urowitz, Murray / van Leeuw, Bernadette / Vasconcelos, Carlos / Voss, Anne / Werth, Victoria P / Zakharova, Helena / Zoma, Asad / Schneider, Matthias / Ward, Michael. ·Department of Medicine, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), Karolinska Institutet, D1:00 Karolinska University Hospital, Solna, Stockholm, Sweden. · Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The Netherlands. · Department of Rheumatology, Clinical Immunology and Allergy, University of Crete School of Medicine, Iraklion, Greece. · Feinstein Institute for Medical Research, Manhasset, New York, USA. · Department of Medicine III, University Medical Center TU Dresden, Dresden, Germany. · New York University, New York, USA. · LPRe SR-Klub Motýlik, Bratislava, Slovakia. · Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. · Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Department of Medicine and Joint Academic Rheumatology Program Medical School, National and Kapodestrian University of Athens, Athens, Greece. · NIHR Manchester Biomedical Research Unit, The University of Manchester and Central Manchester Foundation Trust, Manchester, UK. · Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Catalonia, Spain. · Division of Rheumatology, The Arthritis Society Chair in Rheumatic Diseases Cumming School of Medicine University of Calgary, Calgary, Alberta, Canada. · Lupus Foundation of America, Washington DC, USA. · Université Paris-Decartes, Paris, France. · AP-HP, Hôpital Cochin, service de médecine interne, centre de reference maladies auto-immunes et systémiques rares, Paris, France. · Department of Rheumatology and Immunology, Institute of Bioanalysis, Institute of Family Medicine, University of Pécs, Pécs, Hungary. · Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary. · Department Rheumatology and Clinical Immunology, University Medical Center, Utrecht, The Netherlands. · Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italy. · Department Medicine/Rheumatology and Clinical Immunology, Charite Universitätsmedizin Berlin, Berlin, Germany. · Polyclinic of Rheumatology, Hiller Research Unit, University Clinic Duesseldorf, Heinrich-Heine-University, Duesseldorf, Germany. · Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. · Division of Rheumatology, Medical University of Graz, Graz, Austria. · Service de Rhumatologie, Cliniques universitaires Saint-Luc, Pôle de pathologies rhumatismales inflammatoires et systémiques, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Bruxelles, Belgium. · Department of Medicine, The Centre for Rheumatology, University College London, UK. · Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Copenhagen, Denmark. · Department of Medicine, University of Cambridge, Cambridge, UK. · Interdisciplinary Center for Clinical Trials (IZKS), University Medical Center Mainz, Mainz, Germany. · LUPUS EUROPE, co-opted trustee for research, Essex UK. · Rheumatology Department, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. · Université Paris-Sud; Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-sud; INSERM U1184, Le Kremlin Bicêtre, France. · Bone Densitometry Unit, Monla Hospital, Tripoli, Lebanon. · Monash University, Faculty of Medicine, Nursing & Health Sciences, Monash Medical Centre, Clayton, Australia. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. · Department of Internal Medicine, Division of Rheumatology, Istanbul University, Istanbul Medical Faculty, Istanbul, Turkey. · University of Santo Tomas, Manila, Philippines. · Vasculitis.at, Vienna, Austria. · Department of Connective Tissues Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland. · Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. · RNA and Molecular Pathology Research Group, Institute of Medical Biology, Health Science Faculty, University of Tromsø, Tromsø, Norway. · National Institute for Rheumatic Diseases, Piešťany, Slovak Republic. · Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center (Affiliated to Tel-Aviv University), Tel-Aviv, Israel. · Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria. · Dipartimento di Scienze Cliniche e Sperimentali, Università degli Studi di Brescia, U.O. Reumatologia e Immunolgia Clinica, Spedali Civili di Brescia, Brescia, Italy. · Centre for Prognosis Studies in the Rheumatic Diseases, Senior Scientist Krembil Research Institute, Professor Medicine, University of Toronto, Toronto Western Hospital EW 1-409, Toronto, Canada. · Unidade de Imunologia Clínica, Hospital Santo António, Centro Hospitalar do Porto, UMIB, Instituto de Ciencias Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal. · Department of Rheumatology, Odense University Hospital, University of Southern Denmark, Denmark. · Corporal Michael J. Crescenz VA Medical Center (Philadelphia), Philadelphia, Philadelphia, USA. · Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA. · Nephrology Unit, City Clinical Hospital n.a. S.P. Botkin, Moscow, Russia. · Lanarkshire Centre for Rheumatology, Hairmyres Hospital, Scotland, UK. · National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. ·Ann Rheum Dis · Pubmed #27884822.

ABSTRACT: OBJECTIVES: Treat-to-target recommendations have identified 'remission' as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE. METHODS: An international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%. RESULTS: The task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: CONCLUSIONS: The work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.

5 Review Is there a cure for systemic lupus erythematosus? 2013

Rosario, C / Seguro, L / Vasconcelos, C / Shoenfeld, Y. ·Internal Medicine Department, Hospital de Pedro Hispano, Portugal. ·Lupus · Pubmed #23554031.

ABSTRACT: The morbidity and mortality of systemic lupus erythematosus (SLE) is a subject of intense relevance in the literature, yet descriptions of prolonged and sustained remissions or even cure are barely reported. In recent decades the life expectancy in SLE patients has improved, but the quality of life seems to be poor compared with other chronic diseases and with the general population. The immunopathogenesis of SLE is complex and not fully understood, so patients have been treated with nonspecific immunosuppressive therapies. But in recent years, because of advances in basic science, targeted therapies have been developed. Despite the progress made in treating SLE, currently a cure in SLE seems to be a myth. SLE it seems, remains incurable. A specific treatment has not emerged to directly abrogate a disease-specific autoimmune response. Relapsing manifestations and complications of treatment still remain important markers of morbidity.

6 Review Refractory disease in systemic lupus erythematosus. 2011

Campar, Ana / Farinha, Fátima / Vasconcelos, Carlos. ·Santo António Hospital, Internal Medicine Department, Porto, Portugal. anaccampar@hotmail.com ·Autoimmun Rev · Pubmed #21600313.

ABSTRACT: There is no definition or guidelines for refractory disease (RD) in Systemic Lupus Erythematosus (SLE). However, new therapies have been tested mainly in refractory patients. The concept, like the disease, is complex and implies deeper knowledge on the disease pathogenesis and patients' subsets. RD is not included in current activity indices of the disease, what raises the question of how are we monitoring its response to new drugs. In this paper, we analyse some concepts considered important for the global definition of RD in SLE and in some specific organ involvements, excluding lupus nephritis. Management issues will be addressed also. Finally, we review therapeutic options in particular subsets of the disease, namely, cutaneous, articular, haematological and neuropsychiatric lupus. Crucial to the management of a patient suspected to be refractory is an accurate diagnosis, assuring that the persistent clinical manifestations are derived primarily from SLE and not from a concomitant or alternative process. Likewise, certainty about the patient compliance with the therapy prescribed is a frequent unrecognized problem that erroneously might lead to a classification of RD. Therapy of RD for SLE, in general and in most particular involvements, is currently based mainly on the clinician's own experience and judgement, with few randomized trials effectively addressing the issue. In such a heterogeneous disease, consideration of approval of drugs for single-organ indications may pave the way for new therapies. Better biomarkers are needed to add accuracy to the currently used activity indices in order to monitor RD and consolidate its definition. Prospective studies directed to RD in the main SLE involvements are needed to improve our understanding on the management of the disease and foster the development of targeted new drugs.

7 Review Pregnancy and systemic lupus erythematosus: review of clinical features and outcome of 51 pregnancies at a single institution. 2010

Carvalheiras, Graziela / Vita, Pedro / Marta, Susana / Trovão, Rita / Farinha, Fátima / Braga, Jorge / Rocha, Guilherme / Almeida, Isabel / Marinho, António / Mendonça, Teresa / Barbosa, Paulo / Correia, João / Vasconcelos, Carlos. ·Serviço de Medicina, Centro Hospitalar do Porto, Hospital Santo António, Porto, Portugal. grazielacarvalheiras@sapo.pt ·Clin Rev Allergy Immunol · Pubmed #19603147.

ABSTRACT: Systemic lupus erythematosus (SLE) is mainly a disease of fertile women and the coexistence of pregnancy is by no means a rare event. How SLE and its treatment affects pregnancy outcome is still a matter of debate. Assessment of the reciprocal clinical impact of SLE and pregnancy was investigated in a cohort study. We reviewed the clinical features, treatment, and outcomes of 43 pregnant SLE patients with 51 pregnancies followed from 1993 to 2007 at a tertiary university hospital. The age of patients was 28.7 +/- 5.4 years and SLE was diagnosed at age of 23.0 +/- 6.1 years. Previous manifestations of SLE included lupus nephritis (14 patients) and secondary antiphospholipid syndrome (11 patients). Thirty-five pregnant patients (69%) were in remission for more than 6 months at the onset of pregnancy. Patients were being treated with low doses of prednisone (29), hydroxychloroquine (20), azathioprine (five), acetylsalicylic acid (51), and low molecular weight heparin (13). Sixteen pregnancy-associated flares were documented, mainly during the second trimester (42%) and also in the following year after delivery (25%). Renal involvement was found in 11 cases (68%). Spontaneous abortion occurred in 6%, 16% had premature deliveries, and 74% were delivered at term. No cases of maternal mortality occurred. No cases of fetal malformation were recorded. There was one intrauterine fetal death and one neonatal death at 24 gestational weeks. Pregnant women with SLE are high risk patients, but we had a 90% success rate in our cohort. A control disease activity strategy to target clinical remission is essential.

8 Clinical Trial Vitamin D supplementation effects on FoxP3 expression in T cells and FoxP3 2017

Marinho, António / Carvalho, Cláudia / Boleixa, Daniela / Bettencourt, Andreia / Leal, Bárbara / Guimarães, Judite / Neves, Esmeralda / Oliveira, José Carlos / Almeida, Isabel / Farinha, Fátima / Costa, Paulo P / Vasconcelos, Carlos / Silva, Berta M. ·UMIB, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), UPorto, Porto, Portugal. antmarinho@hotmail.com. · Unidade Imunologia Clínica, Centro Hospitalar do Porto, Hospital Santo António, Largo Prof. Abel Salazar, 4099-001, Porto, Portugal. antmarinho@hotmail.com. · UMIB, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), UPorto, Porto, Portugal. · Serviço de Imunologia, Centro Hospitalar do Porto, Hospital Santo António, Porto, Portugal. · Departamento de Patologia Clínica, Centro Hospitalar do Porto, Hospital Santo António, Porto, Portugal. · Unidade Imunologia Clínica, Centro Hospitalar do Porto, Hospital Santo António, Largo Prof. Abel Salazar, 4099-001, Porto, Portugal. ·Immunol Res · Pubmed #27423437.

ABSTRACT: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multi-organ inflammation, linked to loss of immune tolerance to self-antigens and the production of a diversity of autoantibodies, with a negative impact on the patients' quality of life. Regulatory T cells have been reported as deficient in number and function in SLE patients. However, some authors also described an enrichment of this cell type. The hypothesis that certain forms of autoimmunity may result from a conversion of Treg cells into a Th17 cell phenotype has been suggested by some studies. In fact, in SLE patients' sera, the IL-17 levels were observed as abnormally high when compared with healthy individuals. Environmental factors, such as vitamin D, that is considered a potential anti-inflammatory agent, combined with genetic and hormonal characteristics have been associated with SLE phenotype and with disease progression. The aim of this study was to evaluate the effect of vitamin D supplementation on FoxP3 expression and IL-17A-producing T cells, through FoxP3

9 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

10 Article Two separate effects contribute to regulatory T cell defect in systemic lupus erythematosus patients and their unaffected relatives. 2017

Costa, N / Marques, O / Godinho, S I / Carvalho, C / Leal, B / Figueiredo, A M / Vasconcelos, C / Marinho, A / Moraes-Fontes, M F / Gomes da Costa, A / Ponte, C / Campanilho-Marques, R / Cóias, T / Martins, A R / Viana, J F / Lima, M / Martins, B / Fesel, C. ·Instituto Gulbenkian de Ciência, Oeiras, Portugal. · UMIB, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Portugal. · Hospital de Santo António, Centro Hospitalar do Porto, Unidade Imunologia Clínica, Porto, Portugal. · Hospital de Curry Cabral, Centro Hospitalar de Lisboa Central, Unidade de Doenças Auto-imunes, Lisbon, Portugal. · Hospital de Santa Maria, Lisbon, Portugal. · Instituto Português de Reumatologia, Lisbon, Portugal. · Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal. ·Clin Exp Immunol · Pubmed #28542701.

ABSTRACT: Forkhead box P3 (FoxP3)

11 Article Alveolar hemorrhage in systemic lupus erythematosus: a cohort review. 2016

Andrade, C / Mendonça, T / Farinha, F / Correia, J / Marinho, A / Almeida, I / Vasconcelos, C. ·Internal Medicine, Hospital Pedro Hispano, Matosinhos, Portugal carina82andrade@gmail.com. · Clinical Immunology Unit, Centro Hospitalar do Porto and UMIB, ICBAS, Universidade do Porto, Portugal. ·Lupus · Pubmed #26385219.

ABSTRACT: Diffuse alveolar hemorrhage (DAH) is a rare but potentially catastrophic manifestation with a high mortality. Among rheumatologic diseases, it occurs most frequently in patients with systemic lupus erythematosus (SLE) and systemic vasculitis. Despite new diagnostic tools and therapies, it remains a diagnostic and therapeutic challenge. The aim of this work was to characterize the SLE patients with an episode of alveolar hemorrhage followed in our Clinical Immunology Unit (CIU). A retrospective chart review was carried out for all patients with SLE followed in CIU between 1984 and the end of 2013. We reviewed the following data: demographic characteristics, clinical and laboratory data, radiologic investigations, histologic studies, treatment, and outcome. We identified 10 episodes of DAH, corresponding to seven patients, all female. These represent 1.6% of SLE patients followed in our Unit. The age at DAH attack was 42.75 ± 18.9 years. The average time between diagnosis of SLE and the onset of DAH was 7.1 years. Three patients had the diagnosis of SLE and the DAH attack at the same time. Disease activity according to SLEDAI was high, ranging from 15 to 41. All patients were treated with methylprednisolone, 37.5% cyclophosphamide and 28.6% plasmapheresis. The overall mortality rate was 28.6%.

12 Article Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis. 2016

Tamirou, Farah / D'Cruz, David / Sangle, Shirish / Remy, Philippe / Vasconcelos, Carlos / Fiehn, Christoph / Ayala Guttierez, Maria del Mar / Gilboe, Inge-Magrethe / Tektonidou, Maria / Blockmans, Daniel / Ravelingien, Isabelle / le Guern, Véronique / Depresseux, Geneviève / Guillevin, Loïc / Cervera, Ricard / Houssiau, Frédéric A / Anonymous351036. ·Rheumatology Department, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium. · Louise Coote Lupus Unit, St Thomas' Hospital, London, UK. · Nephrology Department, Hôpital Henri Mondor, Créteil, France. · Clinical Immunology Unit, Hospital Santo Antonio, ICBAS, Porto, Portugal. · ACURA Center for Rheumatic Diseases, Baden-Baden, Germany. · Department of General Internal Medicine, Hospital Regional Universitario Carlos Haya, Malaga, Spain. · Rheumatology Department, Rikshospitalet University Hospital, Oslo, Norway. · First Department of Internal Medicine, National University of Athens, Athens, Greece. · General Internal Medicine Department, UZ Gasthuisberg, Katholieke Universiteit Leuven, Leuven, Belgium. · Rheumatology Department, Onze-Lieve-Vrouw Ziekenhuis, Aalst, Belgium. · General Internal Medicine Department, Hôpital Cochin, Paris, France. · Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Catalonia, Spain. ·Ann Rheum Dis · Pubmed #25757867.

ABSTRACT: OBJECTIVE: To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome. METHODS: In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up. RESULTS: Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker. CONCLUSIONS: The long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome. TRIAL REGISTRATION NUMBER: NCT00204022.

13 Article Association between vitamin D receptor (VDR) gene polymorphisms and systemic lupus erythematosus in Portuguese patients. 2015

Carvalho, C / Marinho, A / Leal, B / Bettencourt, A / Boleixa, D / Almeida, I / Farinha, F / Costa, P P / Vasconcelos, C / Silva, B M. ·UMIB - Instituto de Ciências Biomédicas de Abel Salazar (ICBAS) - UPorto, Porto, Portugal. · UMIB - Instituto de Ciências Biomédicas de Abel Salazar (ICBAS) - UPorto, Porto, Portugal Unidade Imunologia Clínica, Centro Hospitalar do Porto, Hospital Santo António, Porto, Portugal. · UMIB - Instituto de Ciências Biomédicas de Abel Salazar (ICBAS) - UPorto, Porto, Portugal bertams@icbas.up.pt. ·Lupus · Pubmed #25661837.

ABSTRACT: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, in which both genetic and environmental factors are involved. One such environmental factor is vitamin D, a vital hormone that plays a specific function in the immune system homeostasis, acting through a nuclear receptor (VDR) expressed in all immune cells. Several polymorphisms of the gene that encodes this receptor have been described. Though inconsistently, these polymorphisms have been associated with clinical manifestations and SLE development.The aim of this study was to determine the possible association between VDR gene polymorphisms (BsmI, ApaI, TaqI e FokI) and SLE susceptibility and severity, in a cohort of lupus patients from the north of Portugal.A total of 170 patients (F = 155, M = 15; age = 45 ± 13.4 years) with SLE (diagnosed according the American College of Rheumatology criteria) with at least five years of disease evolution and followed in the Autoimmune Disease Clinical Immunology Unit of Centro Hospitalar do Porto were studied. Patients and 192 ethnicity-matched controls were genotyped for BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms by TaqMan allelic discrimination assay. Disease severity was assessed by SLICC damage score, number of affected organs, number of severe flares and pharmacological history.SLE patients with the CT genotype of FokI polymorphism have a higher SLICC value (p = 0.031). The same result was observed for the group of patients with the TT genotype of TaqI polymorphism (p = 0.046). No differences were observed in VDR genotype between patients and controls. Also, we observed that the other clinical features analysed were not influenced by VDR polymorphisms.Our study confirms a possible role of VDR gene polymorphisms in SLE. A positive association was found between VDR polymorphisms and SLE severity (chronic damage). The presence of CT genotype of FokI and TT genotype of TaqI seems to confer a worse prognosis and may constitute a risk factor for higher long-term cumulative damage in SLE patients.

14 Article PXK locus in systemic lupus erythematosus: fine mapping and functional analysis reveals novel susceptibility gene ABHD6. 2015

Oparina, Nina Y / Delgado-Vega, Angelica M / Martinez-Bueno, Manuel / Magro-Checa, César / Fernández, Concepción / Castro, Rafaela Ortega / Pons-Estel, Bernardo A / D'Alfonso, Sandra / Sebastiani, Gian Domenico / Witte, Torsten / Lauwerys, Bernard R / Endreffy, Emoke / Kovács, László / Escudero, Alejandro / López-Pedrera, Chary / Vasconcelos, Carlos / da Silva, Berta Martins / Frostegård, Johan / Truedsson, Lennart / Martin, Javier / Raya, Enrique / Ortego-Centeno, Norberto / de Los Angeles Aguirre, Maria / de Ramón Garrido, Enrique / Palma, María-Jesús Castillo / Alarcon-Riquelme, Marta E / Kozyrev, Sergey V. ·Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · Centro de Genómica e Investigación Oncológica (GENYO). Pfizer-Universidad de Granada-Junta de Andalucía, PTS, Granada, Spain. · Department of Rheumatology, Hospital Universitario San Cecilio, Granada, Spain. · Unidad de Enfermedades Autoimmunes Sistémicas, UGC Medicina Interna, Hospital Universitario San Cecilio, Granada, Spain. · Servicio de Reumatologia, Hospital Universitario Reina Sofía, Instituto Maimónides de Investigación Biomédica IMIBIC, Córdoba, Spain. · Department of Rheumatology, Sanatorio Parque, Rosario, Argentina. · Department of Health Sciences and IRCAD, University of Eastern Piedmont, Novara, Italy. · Unità Operativa Complessa Reumatología, Azienda Ospedaliera San Camillo- Forlanini, Roma, Italy. · Hannover Medical School, Hannover, Germany. · Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Bruxells, Belgium. · Department of Pediatrics and Health Center, University of Szeged, Szeged, Hungary. · Department of Rheumatology, Albert Szent-Györgyi Clinical Centre, University of Szeged, Szeged, Hungary. · Centro Hospitalar do Porto/Hospital Santo Antonio and UMIB/ICBAS, Porto, Portugal. · IMM, Unit of Immunology and Chronic disease, Karolinska Institutet, Stockholm, Sweden. · Department of Laboratory Medicine, Section of M.I.G., Lund University, Lund, Sweden. · Instituto de Biomedicina y Parasitología López Neyra, CSIC, Armilla, Spain. · Department of Medicine, Hospital Carlos Haya, Málaga, Spain. · Department of Internal Medicine, Hospital Universitario Virgen del Rocío, Seville, Spain. · Centro de Genómica e Investigación Oncológica (GENYO). Pfizer-Universidad de Granada-Junta de Andalucía, PTS, Granada, Spain Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. ·Ann Rheum Dis · Pubmed #24534757.

ABSTRACT: OBJECTIVES: To perform fine mapping of the PXK locus associated with systemic lupus erythematosus (SLE) and study functional effects that lead to susceptibility to the disease. METHODS: Linkage disequilibrium (LD) mapping was conducted by using 1251 SNPs (single nucleotide polymorphism) covering a 862 kb genomic region on 3p14.3 comprising the PXK locus in 1467 SLE patients and 2377 controls of European origin. Tag SNPs and genotypes imputed with IMPUTE2 were tested for association by using SNPTEST and PLINK. The expression QTLs data included three independent datasets for lymphoblastoid cells of European donors: HapMap3, MuTHER and the cross-platform eQTL catalogue. Correlation analysis of eQTLs was performed using Vassarstats. Alternative splicing for the PXK gene was analysed on mRNA from PBMCs. RESULTS: Fine mapping revealed long-range LD (>200 kb) extended over the ABHD6, RPP14, PXK, and PDHB genes on 3p14.3. The highly correlated variants tagged an SLE-associated haplotype that was less frequent in the patients compared with the controls (OR=0.89, p=0.00684). A robust correlation between the association with SLE and enhanced expression of ABHD6 gene was revealed, while neither expression, nor splicing alterations associated with SLE susceptibility were detected for PXK. The SNP allele frequencies as well as eQTL pattern analysed in the CEU and CHB HapMap3 populations indicate that the SLE association and the effect on ABHD6 expression are specific to Europeans. CONCLUSIONS: These results confirm the genetic association of the locus 3p14.3 with SLE in Europeans and point to the ABHD6 and not PXK, as the major susceptibility gene in the region. We suggest a pathogenic mechanism mediated by the upregulation of ABHD6 in individuals carrying the SLE-risk variants.

15 Article Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. 2015

Cervera, R / Serrano, R / Pons-Estel, G J / Ceberio-Hualde, L / Shoenfeld, Y / de Ramón, E / Buonaiuto, V / Jacobsen, S / Zeher, M M / Tarr, T / Tincani, A / Taglietti, M / Theodossiades, G / Nomikou, E / Galeazzi, M / Bellisai, F / Meroni, P L / Derksen, R H W M / de Groot, P G D / Baleva, M / Mosca, M / Bombardieri, S / Houssiau, F / Gris, J-C / Quéré, I / Hachulla, E / Vasconcelos, C / Fernández-Nebro, A / Haro, M / Amoura, Z / Miyara, M / Tektonidou, M / Espinosa, G / Bertolaccini, M L / Khamashta, M A / Anonymous70783. ·Departament of Autoimmune Diseases, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain. · Lupus Unit, Rayne Institute, St Thomas' Hospital, London, UK. · Zabludowicz Centre for Autoimmune Diseases, Chaim-Sheba Medical Centre, Sackler Faculty of Medicine Tel Aviv University, Tel-Hashomer, Israel. · Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Hospital Carlos Haya, Málaga, Spain. · Departament of Infectious Diseases and Rheumatology, Copenhagen University Hospital at Rigshospitalet, Copenhagen, Denmark. · 3rd Departament of Medicine, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary. · Servizio di Inmunologia Clinica e Allergologia, Spedali Civili, Azienda Ospidaliera, Brescia, Italy. · Transfusion and Haemophilia Centre, Hippocration Hospital, Athens, Greece. · Unità Operativa Complessa di Reumatologia, Azienda Ospedaliera Universitaria Senese, Siena, Italy. · Allergy and Clinical Immunology Unit, Dipartimento di Medicina Interna, IRCCS Istituto Auxologico, Università di Milano, Milan, Italy. · Department of Rheumatology and Clinical Immunology, University Medical Centre, Utrecht, The Netherlands. · Department of Haematology, Laboratory of Thrombosis and Haemostasis, University Medical Centre, Utrecht, The Netherlands. · Laboratory of Clinical Immunology, Clinical Centre of Allergology, Medical University, Sofia, Bulgaria. · Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. · Service de Rhumatologie, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. · Laboratoire dHématologie, CHU, Nîmes, France. · Service de Médecine Interne, Hôpital Claude Huriez, Université Lille Nord-de-France, Lille, France. · Unidade de Imunologia Clínica, Hospital Santo António, Centro Hospitalar do Porto and UMIB, ICBAS, Universidade do Porto, Portugal. · Department of Rheumatology, Hospital Regional Universitario de Málaga, University of Málaga, IBIMA, Málaga, Spain. · Department of Internal Medicine, French National Reference Center for Lupus and Antiphospholipid Syndrome, Hôpital Pitié-Salpetrière, Paris, France. · First Department of Internal Medicine, University of Athens School of Medicine, Athens, Greece. ·Ann Rheum Dis · Pubmed #24464962.

ABSTRACT: OBJECTIVES: To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later. METHODS: In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10 years. RESULTS: 53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10 years was 90.7%. CONCLUSIONS: Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.

16 Article CCR5-Delta32: implications in SLE development. 2014

Carvalho, C / Calvisi, S L / Leal, B / Bettencourt, A / Marinho, A / Almeida, I / Farinha, F / Costa, P P / Silva, B M / Vasconcelos, C. ·UMIB, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS) UPorto, Porto, Portugal. ·Int J Immunogenet · Pubmed #24164722.

ABSTRACT: Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease with strong genetic and environmental components. Previous studies have shown increased levels of several chemokines in active SLE. C-C chemokine receptor type 5 (CCR5) is involved in the recruitment of inflammatory cells into tissues, and mechanisms modulating CCR5 expression and function may interfere in SLE development, influencing the clinical course of the disease. The aim of this study was to evaluate the possible association between the CCR5∆32 base-pair deletion polymorphism and SLE disease in a group of Portuguese patients. A total of 219 patients with SLE and 205 healthy individuals were studied. The frequency of CCR5/∆32 heterozygotes was lower in patients with SLE than in controls (8% vs. 15% OR = 0.5162; P = 0.0319), suggesting a protective association between CCR5∆32 allele and SLE. These results highlight the protective role of Th1 cells that express CCR5 in SLE pathogenesis.

17 Article Broadened T-cell repertoire diversity in ivIg-treated SLE patients is also related to the individual status of regulatory T-cells. 2013

Costa, Nuno / Pires, Ana E / Gabriel, Ana M / Goulart, Luiz F / Pereira, Clara / Leal, Bárbara / Queiros, Ana C / Chaara, Wahiba / Moraes-Fontes, Maria F / Vasconcelos, Carlos / Ferreira, Carlos / Martins, Jorge / Bastos, Marina / Santos, Maria J / Pereira, Maria A / Martins, Berta / Lima, Margarida / João, Cristina / Six, Adrien / Demengeot, Jocelyne / Fesel, Constantin. ·Instituto Gulbenkian de Ciência, Apartado 14, 2781-901, Oeiras, Portugal. ·J Clin Immunol · Pubmed #23064977.

ABSTRACT: PURPOSE: Intravenous IgG (ivIg) is a therapeutic alternative for lupus erythematosus, the mechanism of which remains to be fully understood. Here we investigated whether ivIg affects two established sub-phenotypes of SLE, namely relative oligoclonality of circulating T-cells and reduced activity of CD4 + Foxp3+ regulatory T-cells (Tregs) reflected by lower CD25 surface density. METHODS: We conducted a longitudinal study of 15 lupus patients (14 with SLE and one with discoid LE) treated with ivIg in cycles of 2-6 consecutive monthly infusions. Among these 15 patients, 10 responded to ivIg therapy with clear clinical improvement. We characterized Tregs and determined TCR spectratypes of four Vβ families with reported oligoclonality. Cell counts, cytometry and TCR spectratypes were obtained from peripheral blood at various time points before, during and after ivIg treatment. T-cell oligoclonality was assessed as Vβ-familywise repertoire perturbation, calculated for each patient in respect to an individual reference profile averaged over all available time points. RESULTS: For 11 out of 15 patients, average Vβ1/Vβ2/Vβ11/Vβ14 repertoires were less perturbed under than outside ivIg therapy. The four exceptions with relatively increased average perturbation during ivIg therapy included three patients who failed to respond clinically to an ivIg therapy cycle. Patients' Treg CD25 surface density (cytometric MFI) was clearly reduced when compared to healthy controls, but not obviously influenced by ivIg. However, patients' average Treg CD25 MFI was found negatively correlated with both Vβ11 and Vβ14 perturbations measured under ivIg therapy. CONCLUSIONS: This indicates a role of active Tregs in the therapeutic effect of ivIg.

18 Article Fine mapping and conditional analysis identify a new mutation in the autoimmunity susceptibility gene BLK that leads to reduced half-life of the BLK protein. 2012

Delgado-Vega, Angélica M / Dozmorov, Mikhail G / Quirós, Manuel Bernal / Wu, Ying-Yu / Martínez-García, Belén / Kozyrev, Sergey V / Frostegård, Johan / Truedsson, Lennart / de Ramón, Enrique / González-Escribano, María F / Ortego-Centeno, Norberto / Pons-Estel, Bernardo A / D'Alfonso, Sandra / Sebastiani, Gian Domenico / Witte, Torsten / Lauwerys, Bernard R / Endreffy, Emoke / Kovács, László / Vasconcelos, Carlos / da Silva, Berta Martins / Wren, Jonathan D / Martin, Javier / Castillejo-López, Casimiro / Alarcón-Riquelme, Marta E. ·Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, 751 85, Sweden. ·Ann Rheum Dis · Pubmed #22696686.

ABSTRACT: OBJECTIVES: To perform fine mapping of the autoimmunity susceptibility gene BLK and identify functional variants involved in systemic lupus erythematosus (SLE). METHODS: Genotyping of 1163 European SLE patients and 1482 controls and imputation were performed covering the BLK gene with 158 single-nucleotide polymorphisms. Logistic regression analysis was done using PLINK and conditional analyses using GENABEL's test score. Transfections of BLK constructs on HEK293 cells containing the novel mutation or the wild type form were analysed for their effect on protein half-life using a protein stability assay, cycloheximide and western blot. CHiP-qPCR for detection of nuclear factor κ B (NFkB) binding. RESULTS: Fine mapping of BLK identified two independent genetic effects with functional consequences: one represented by two tightly linked associated haplotype blocks significantly enriched for NFκB-binding sites and numerous putative regulatory variants whose risk alleles correlated with low BLK mRNA levels. Binding of NFkBp50 and p65 to an associated 1.2 Kb haplotype segment was confirmed. A second independent genetic effect was represented by an Ala71Thr, low-frequency missense substitution with an OR=2.31 (95% CI 1.38 to 3.86). The 71Thr decreased BLK protein half-life. CONCLUSIONS: These results show that rare and common regulatory variants in BLK are involved in disease susceptibility and both, albeit independently, lead to reduced levels of BLK protein.

19 Article Systemic lupus erythematosus, progressive multifocal leukoencephalopathy, and T-CD4+ lymphopenia. 2012

Brandão, Mariana / Damásio, Joana / Marinho, António / da Silva, Ana Martins / Vasconcelos, Júlia / Neves, Esmeralda / Almeida, Isabel / Farinha, Fátima / Vasconcelos, Carlos. ·Unidade de Imunologia Clínica, Department of Medicine, Hospital de Santo António, Centro Hospitalar do Porto, Largo do Professor Abel Salazar, nº 2, 4099-001, Porto, Portugal. mabrsi@gmail.com ·Clin Rev Allergy Immunol · Pubmed #22674017.

ABSTRACT: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by the reactivation of JC virus and occurs in patients with severe primary or secondary immunosuppression. Recently, PML is becoming relevant in autoimmune disorders, particularly in patients treated with biologic agents. However, systemic lupus erythematosus (SLE) appears to be associated with susceptibility to PML that cannot be entirely explained by the immunosuppressive therapy. The authors present two patients with the diagnosis of SLE and PML: One had a heavy immunosuppressive therapy history, and the other had never experienced biologic or cytotoxic therapeutics. Both patients had a profound T-CD4+ lymphopenia during their clinical history. These two cases emphasize the importance of CD4+ lymphopenia in SLE patients with and without immunosuppressors regarding opportunistic infections.

20 Article Compensatory T-cell regulation in unaffected relatives of SLE patients, and opposite IL-2/CD25-mediated effects suggested by coreferentiality modeling. 2012

Fesel, Constantin / Barreto, Marta / Ferreira, Ricardo C / Costa, Nuno / Venda, Lara L / Pereira, Clara / Carvalho, Claudia / Morães-Fontes, Maria Francisca / Ferreira, Carlos M / Vasconcelos, Carlos / Viana, João F / Santos, Eugenia / Martins, Berta / Demengeot, Jocelyne / Vicente, Astrid M. ·Instituto Gulbenkian de Ciência, Oeiras, Portugal. cfesel@igc.gulbenkian.pt ·PLoS One · Pubmed #22479496.

ABSTRACT: In human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4(+)CD25(bright) T-cells that were regularly 70-90% Foxp3(+). We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with the individual autoantibody production. To study this further, we applied a novel analytic approach named coreferentiality that tests the indirect relatedness of parameters in respect to multivariate phenotype data. Results show that independently of their direct correlation, aTreg frequencies and specific SLE-associated IgG were likely functionally related in unaffected relatives: they significantly parallelled each other in their relations to broad-range immunoblot autoantibody profiles. In unaffected relatives, we also found coreferential effects of genetic variation in the loci encoding IL-2 and CD25. A model of CD25 functional genetic effects constructed by coreferentiality maximization suggests that IL-2-CD25 interaction, likely stimulating aTregs in unaffected relatives, had an opposed effect in SLE patients, presumably triggering primarily T-effector cells in this group. Coreferentiality modeling as we do it here could also be useful in other contexts, particularly to explore combined functional genetic effects.

21 Article Are cognitive and olfactory dysfunctions in neuropsychiatric lupus erythematosus dependent on anxiety or depression? 2012

Cavaco, Sara / Martins da Silva, Ana / Santos, Ernestina / Coutinho, Ester / Marinho, António / Moreira, Inês / Gonçalves, Alexandra / Pinto, Cláudia / Teixeira-Pinto, Armando / Vasconcelos, Carlos. ·Hospital S. António, Serviço de Neurologia, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal. saramscavaco@gmail.com ·J Rheumatol · Pubmed #22382338.

ABSTRACT: OBJECTIVE: Depressed mood and cognitive impairments are common findings in systemic lupus erythematosus (SLE) and frequently coexist. We assessed the neuropsychological functioning of patients with SLE and investigated its association with psychopathological symptoms. METHODS: A total of 85 patients with SLE (28 with neuropsychiatric syndromes: NPSLE) and 85 healthy control subjects with similar demographic characteristics were asked to perform a series of neuropsychological tests. A self-report questionnaire (the Hospital Anxiety and Depression Scale) was used to screen for psychopathology symptoms. Patients with SLE underwent a neurological examination. RESULTS: Patients with NPSLE were more depressed and were more frequently impaired in cognitive and olfactory functions than controls or non-NPSLE patients. The NPSLE group remained statistically different from the other 2 groups on a series of neuropsychological measures (the Auditory Verbal Learning Test, Trail Making Test - Part A, Nine-Hole Peg Test, and Brief Smell Identification Test) even after control for elevated anxiety and depressed mood. Non-NPSLE and control groups were not significantly different regarding either psychopathological symptoms or neuropsychological functioning. CONCLUSION: Verbal memory, psychomotor speed, and olfaction are particularly vulnerable to dysfunction in NPSLE; impairment in these neuropsychological domains is not completely explained by psychopathology symptoms.

22 Article Evaluation of the reactivity of sera from patients with systemic lupus erythematosus against the human MCP1. 2012

Bronze-da-Rocha, Elsa / Nóvoa, Ana / Teixeira, Natércia / Vasconcelos, Carlos Silva / Cerveira, Conceição / Castro e Melo, João / Carvalho, Manuel Cirne. ·Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4050-047, Porto, Portugal. elsa.rocha@ff.up.pt ·J Clin Immunol · Pubmed #22371290.

ABSTRACT: This study evaluates metaphase chromosome protein 1 (MCP1), a nuclear antigen, as a diagnostic marker for systemic lupus erythematosus (SLE). Reactivity of sera from 114 Portuguese patients with autoimmune rheumatic disease or from healthy blood donors (HBD), against MCP1, produced in bacteria (bact-MCP1) or in its native form (native-MCP1), was determined by immunoblotting. Predictive and discriminative power of MCP1 reactivity for SLE diagnosis in disease-control groups was evaluated by logistic regression, its diagnostic value determined by receiver-operating characteristic analysis and compared with similar analysis of antinuclear antibody and double-stranded DNA (dsDNA). We demonstrated that native-MCP1, in contrast to bact-MCP1, reacts with SLE sera with significant predictive and discriminative power versus other autoimmune diseases (odds ratio [OR] ≤3.537 and ≥3.265; area under the receiver-operating characteristic curve [AUC] ≤0.643 and ≥0.636) or versus HBD (OR = 5.006; AUC = 0.671), showing a good diagnostic power with high specificity (82.1% versus HBD) and low sensitivity for SLE, similar to those of dsDNA. The reactivity of SLE sera with native-MCP1 was shown to be dependent on the presence of phosphorylated residues. Native-MCP1 was shown to have diagnostic value as a specific marker for SLE diagnosis and, therefore, is a suitable substrate for a new antibody test. The widely reported importance of phosphorylated epitopes as targets for autoantibodies in SLE could also be confirmed for native-MCP1.

23 Article Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene. 2012

Löfgren, S E / Frostegård, J / Truedsson, L / Pons-Estel, B A / D'Alfonso, S / Witte, T / Lauwerys, B R / Endreffy, E / Kovács, L / Vasconcelos, C / Martins da Silva, B / Kozyrev, S V / Alarcón-Riquelme, M E. ·Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. ·Genes Immun · Pubmed #22218224.

ABSTRACT: A recent genome-wide association study revealed a variant (rs2431697) in an intergenic region, between the pituitary tumor-transforming 1 (PTTG1) and microRNA (miR-146a) genes, associated with systemic lupus erythematosus (SLE) susceptibility. Here, we analyzed with a case-control design this variant and other candidate polymorphisms in this region together with expression analysis in order to clarify to which gene this association is related. The single-nucleotide polymorphisms (SNPs) rs2431697, rs2910164 and rs2277920 were genotyped by TaqMan assays in 1324 SLE patients and 1453 healthy controls of European ancestry. Genetic association was statistically analyzed using Unphased. Gene expression of PTTG1, the miRNAs miR-3142 and primary and mature forms of miR-146a in peripheral blood mononuclear cells (PBMCs) were assessed by quantitative real-time PCR. Of the three variants analyzed, only rs2431697 was genetically associated with SLE in Europeans. Gene expression analysis revealed that this SNP was not associated with PTTG1 expression levels, but with the microRNA-146a, where the risk allele correlates with lower expression of the miRNA. We replicated the genetic association of rs2341697 with SLE in a case-control study in Europeans and demonstrated that the risk allele of this SNP correlates with a downregulation of the miRNA 146a, potentially important in SLE etiology.

24 Article Repeat kidney biopsies fail to detect differences between azathioprine and mycophenolate mofetil maintenance therapy for lupus nephritis: data from the MAINTAIN Nephritis Trial. 2012

Stoenoiu, Maria S / Aydin, Selda / Tektonidou, Maria / Ravelingien, Isabelle / le Guern, Véronique / Fiehn, Christoph / Remy, Philippe / Delahousse, Michel / Petera, Peter / Quémeneur, Thomas / Vasconcelos, Carlos / D'Cruz, David / Gilboe, Inge-Magrethe / Jadoul, Michel / Karras, Alexandre / Depresseux, Geneviève / Guillevin, Loïc / Cervera, Ricard / Cosyns, Jean-Pierre / Houssiau, Frédéric A / Anonymous1960711. ·Department of Rheumatology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. ·Nephrol Dial Transplant · Pubmed #22110048.

ABSTRACT: BACKGROUND: In the MAINTAIN Nephritis Trial, azathioprine (AZA) and mycophenolate mofetil (MMF) were compared as maintenance immunosuppressive treatment of proliferative lupus nephritis (LN) after a short-course of intravenous cyclophosphamide. Here, we compare the pathological findings on repeat kidney biopsies between the two groups. METHODS: Per protocol, repeat renal biopsies were obtained in 30 patients (16 AZA and 14 MMF) at 2 years (±6 months). Baseline and follow-up biopsies were graded according to the International Society of Nephrology/Renal Pathological Society (ISN/RPS) classification. The activity and chronicity indices (AI, CI) were calculated using two different semiquantitative scoring systems (Morel-Maroger and National Institutes of Health). Statistics were performed by non-parametric tests. RESULTS: The clinical characteristics of the 30 re-biopsied patients only marginally differ from the entire MAINTAIN cohort (105 patients). Clinical baseline and follow-up characteristics of AZA- and MMF-treated re-biopsied patients did not differ. Time (SD) to repeat renal biopsy was 25.0 (2.0) and 26.5 (3.3) months in AZA and MMF patients, respectively. More patients had normal renal biopsies or Classes I/II/V LN at follow-up compared to baseline and conversely, less patients had Class IV LN at follow-up. In both groups, the AI statistically decreased at follow-up compared to baseline, while the CI slightly, but significantly, increased. No differences could be detected between the groups. CONCLUSION: Centralized pathological analyses, including ISN/RPS classification and comparisons of AI/CI, failed to find differences between MMF and AZA at 2 years, a result well in line with the absence of difference in long-term clinical outcome reported elsewhere.

25 Article Genetically determined Amerindian ancestry correlates with increased frequency of risk alleles for systemic lupus erythematosus. 2010

Sanchez, Elena / Webb, Ryan D / Rasmussen, Astrid / Kelly, Jennifer A / Riba, Laura / Kaufman, Kenneth M / Garcia-de la Torre, Ignacio / Moctezuma, Jose F / Maradiaga-Ceceña, Marco A / Cardiel-Rios, Mario H / Acevedo, Eduardo / Cucho-Venegas, Mariano / Garcia, Mercedes A / Gamron, Susana / Pons-Estel, Bernardo A / Vasconcelos, Carlos / Martin, Javier / Tusié-Luna, Teresa / Harley, John B / Richardson, Bruce / Sawalha, Amr H / Alarcón-Riquelme, Marta E. ·Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. ·Arthritis Rheum · Pubmed #20848568.

ABSTRACT: OBJECTIVE: To assess whether genetically determined Amerindian ancestry predicts increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus (SLE). METHODS: Single-nucleotide polymorphisms (SNPs) within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation between ancestry and the presence of risk alleles was analyzed using linear regression. RESULTS: A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, ITGAM, and IRF5 were associated with lupus in a Hispanic Mestizo cohort enriched for European and Amerindian ancestry. In addition, 2 SNPs within the major histocompatibility complex region, previously shown to be associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression, we predicted an average increase of 2.34 risk alleles when comparing an SLE patient with 100% Amerindian ancestry versus an SLE patient with 0% Amerindian ancestry (P < 0.0001). SLE patients with 43% more Amerindian ancestry were predicted to carry 1 additional risk allele. CONCLUSION: Our results demonstrate that Amerindian ancestry is associated with an increased number of risk alleles for SLE.

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