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Systemic Lupus Erythematosus: HELP
Articles by Megan E. B. Clowse
Based on 27 articles published since 2008
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Between 2008 and 2019, M. Clowse wrote the following 27 articles about Lupus Erythematosus, Systemic.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review State of the art: Reproduction and pregnancy in rheumatic diseases. 2015

Østensen, Monika / Andreoli, Laura / Brucato, Antonio / Cetin, Irene / Chambers, Christina / Clowse, Megan E B / Costedoat-Chalumeau, Nathalie / Cutolo, Maurizio / Dolhain, Radboud / Fenstad, M H / Förger, Frauke / Wahren-Herlenius, Marie / Ruiz-Irastorza, Guillermo / Koksvik, Hege / Nelson-Piercy, Catherine / Shoenfeld, Yehuda / Tincani, Angela / Villiger, Peter M / Wallenius, Marianne / von Wolff, Michael. ·National Advisory Unit on Pregnancy and Rheumatic Diseases, Department of Rheumatology, St. Olavs Hospital, University Hospital of Trondheim, Norway. Electronic address: monika.ostensen@gmail.com. · Rheumatology and Clinical Immunology, Spedali Civili of Brescia, Department of Clinical and Experimental Sciences, University of Brescia, Italy. · Department of Internal Medicine, Ospedale papa Giovanni XXIII Bergamo, Italy. · Department of Mother and Child, Hospital Luigi Sacco, University of Milano, Italy. · Department of Pediatrics, University of California San Diego, La Jolla, CA 92093-0828, USA. · Division of Rheumatology, Department of Medicine, Duke University Medical Center, Durham, NC, USA. · Université Paris-Descartes, Paris, France; AP-HP, Hôpital Cochin, Centre de référence maladies auto-immunes et systémiques rares, Service de médecine interne, Paris, France. · Research Laboratories and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy. · Department of Rheumatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Immunology and Transfusion Medicine, St. Olavs Hospital, Trondheim, Norway. · Department of Rheumatology and Clinical Immunology/Allergology, University Hospital of Bern, CH-3010 Bern, Switzerland. · Department of Medicine, Centre for Molecular Medicine, Karolinska Universitetssjukhuset, Stockholm, Sweden. · Autoimmune Diseases Research Unit, Department of Internal Medicine, Biocruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Bizkaia, Spain. · National Advisory Unit on Pregnancy and Rheumatic Diseases, Department of Rheumatology, St. Olavs Hospital, University Hospital of Trondheim, Norway. · Women's Health Academic Centre, St Thomas' Hospital, London, UK. · Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer, Israel. · Department of Rheumatology and Clinical Immunology, Ospedale Civile and University of Brescia, Brescia, Italy. · Department of Rheumatology and Clinical Immunology/Allergology, University Hospital of Bern, Bern, Switzerland. · National Service for Pregnancy and Rheumatic Diseases, Department of Rheumatology, Trondheim University Hospital, Trondheim, Norway; Dept of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. · University Women's Hospital, Division of Gynaecological Endocrinology and Reproductive Medicine, University of Berne, Berne, Switzerland. ·Autoimmun Rev · Pubmed #25555818.

ABSTRACT: Throughout the last decade, increasing awareness has been raised on issues related to reproduction in rheumatic diseases including basic research to clarify the important role of estrogens in the etiology and pathophysiology of immune/inflammatory diseases. Sub- or infertility is a heterogeneous condition that can be related to immunological mechanisms, to pregnancy loss, to disease burden, to therapy, and to choices in regard to family size. Progress in reproductive medicine has made it possible for more patients with rheumatic disease to have children. Active disease in women with rheumatoid arthritis (RA) affects their children's birth weight and may have long-term effects on their future health status. Pregnancy complications as preeclampsia and intrauterine growth restriction are still increased in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), however, biomarkers can monitor adverse events, and several new therapies may improve outcomes. Pregnancies in women with APS remain a challenge, and better therapies for the obstetric APS are needed. New prospective studies indicate improved outcomes for pregnancies in women with rare diseases like systemic sclerosis and vasculitis. TNF inhibitors hold promise for maintaining remission in rheumatological patients and may be continued at least in the first half of pregnancy. Pre-conceptional counseling and interdisciplinary management of pregnancies are essential for ensuring optimal pregnancy outcomes.

2 Review Systemic lupus erythematosus and pregnancy outcomes: an update and review of the literature. 2014

Peart, Erica / Clowse, Megan E B. ·Duke University Medical Center, Durham, North Carolina, USA. ·Curr Opin Rheumatol · Pubmed #24419751.

ABSTRACT: PURPOSE OF REVIEW: This review synthesizes new data from the studies published between 2011 and 2013, with particular focus on the different information gleaned by various study types. RECENT FINDINGS: Population-based cohorts have demonstrated that women with systemic lupus erythematosus (SLE) have fewer live births and more pregnancy complications, but can have successful live births after having a poor outcome. A retrospective study suggests that only 4 months, not the traditional 6 months of disease quiescent SLE prior to pregnancy improves outcomes. Prospective studies identified several novel predictors of poor pregnancy outcomes, including uterine Doppler and laboratory findings. A prospective study found great success in transitioning to azathioprine from mycophenolate mofetil prior to pregnancy in patients with quiet lupus nephritis. Two retrospective analyses suggest that hydroxychloroquine may prevent congenital heart block in pregnancies exposed to SSA/Ro antibodies. Finally, the initial pregnancy data for belimumab suggest a high degree of transplacental transfer, but thus far no definitive link between belimumab and congenital abnormalities. SUMMARY: Recent studies suggest both novel markers of poor pregnancy outcomes and new approaches to the management of lupus during pregnancy.

3 Review Pathogenesis of pregnancy complications in systemic lupus erythematosus. 2013

Ostensen, Monika / Clowse, Megan. ·Department of Rheumatology, National Center of Pregnancy and Rheumatic Disease, University Hospital of Trondheim, Trondheim, Norway. monika.ostensen@gmail.com ·Curr Opin Rheumatol · Pubmed #23917157.

ABSTRACT: PURPOSE OF REVIEW: In spite of the advances made in the management of pregnancies in women with systemic lupus erythematosus (SLE), maternal complications and adverse fetal outcomes still exceed the rate of pregnancy complications in the general population. An intriguing question relates to the observation that pregnancy loss, intrauterine growth restriction (IUGR), preterm birth, and preeclampsia remain major complications in SLE pregnancies, not substantially altered by improved therapy and monitoring. RECENT FINDINGS: From the review of the recent literature on the pathogenesis of pregnancy loss, IUGR, preeclampsia, and prematurity, it appears that clinical or subclinical inflammation, presence of autoantibodies, hormonal dysfunction, and immune alterations of lupus contribute to pregnancy complications. Impairment of early placenta development leads to poor vascularization, resulting in placental ischemia and subsequent endothelial damage. Depending on the extent of the pathological process, pregnancy loss, IUGR, and preeclampsia can develop. SUMMARY: Early recognition of pregnancy complications is desirable in order to prevent their development or to prompt intervention that improves the outcomes. Several biomarkers have been investigated for their ability to predict complications at an early stage of pregnancy. However, up to date only lupus anticoagulant has emerged as a consistent predictor for adverse pregnancy outcomes.

4 Review Managing contraception and pregnancy in the rheumatologic diseases. 2010

Clowse, Megan E B. ·Department of Rheumatology & Immunology Duke University Health System, Durham, UK. Megan.clowse@duke.edu ·Best Pract Res Clin Rheumatol · Pubmed #20534371.

ABSTRACT: Most pregnancies in women with rheumatologic disease will result in the delivery of a healthy baby. Pregnancy can be particularly risky in women with active disease or on teratogenic medications, making contraception an important issue for these women. All women with rheumatologic disease have contraceptive options, including barrier methods, the intra-uterine device and progesterone-only medications. Active inflammatory disease, whether in the form of lupus, systemic vasculitis or myositis, places the pregnancy at increased risk. Pre-eclampsia is a particular risk for women with lupus or antiphospholipid syndrome and may be decreased by daily low-dose aspirin. Rheumatoid arthritis typically improves and does not have a major impact on pregnancy outcomes. The expected post-partum arthritis flare may be avoided by restarting medications soon after delivery. Judicious use of medication and close observation may be the keys to successful pregnancy in women with rheumatologic disease.

5 Clinical Trial Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials. 2017

Clowse, Megan E B / Wallace, Daniel J / Furie, Richard A / Petri, Michelle A / Pike, Marilyn C / Leszczyński, Piotr / Neuwelt, C Michael / Hobbs, Kathryn / Keiserman, Mauro / Duca, Liliana / Kalunian, Kenneth C / Galateanu, Catrinel / Bongardt, Sabine / Stach, Christian / Beaudot, Carolyn / Kilgallen, Brian / Gordon, Caroline / Anonymous3470880. ·Duke University Medical Center, Durham, North Carolina. · Cedars-Sinai Medical Center, Los Angeles, California. · Northwell Health, New York, New York. · Johns Hopkins University School of Medicine, Baltimore, Maryland. · MedPharm Consulting, Cambridge, Massachusetts. · Poznan University of Medical Sciences, Poznan, Poland. · Alameda County Health System, Oakland, California. · Denver Arthritis Clinic, Denver, Colorado. · Pontifical Catholic University, Porto Alegre, Brazil. · Clinica Neomed, Brasov, Romania. · University of California San Diego School of Medicine, La Jolla. · UCB Pharma, Brussels, Belgium. · UCB Pharma, Monheim, Germany. · UCB Pharma, Raleigh, North Carolina. · University of Birmingham and University Hospital Birmingham NHS Foundation Trust, Birmingham, UK. ·Arthritis Rheumatol · Pubmed #27598855.

ABSTRACT: OBJECTIVE: Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). METHODS: Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti-double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5-60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders. RESULTS: In the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified. CONCLUSION: In patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.

6 Clinical Trial Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of SBI-087, a CD20-Directed B-cell Depleting Agent: Phase 1 Dose Escalating Studies in Patients With Either Mild Rheumatoid Arthritis or Systemic Lupus. 2016

Cohen, Stanley / Clowse, Megan / Pardo, Patricia / Bhattacharya, Indranil / Menon, Sandeep / Gourley, Ian / Diehl, Annette. ·Metroplex Clinical Research Center, Dallas, Texas. Electronic address: arthdoc@aol.com. · Department of Medicine, Division of Rheumatology and Immunology, Duke University, Durham, North Carolina. · Miami Research Associates, South Miami, Florida. · Pfizer Inc, Cambridge, Massachusetts. · Janssen, Spring House, Pennsylvania. · Pfizer Inc, Collegeville, Pennsylvania. ·Clin Ther · Pubmed #27112532.

ABSTRACT: PURPOSE: SBI-087 is a Small Modular Immunopharmaceutical Protein™(SMIP™) drug that binds to CD20 and has been reported to deplete B cells in murine/primate studies. The safety, tolerability and pharmacokinetic/pharmacodynamic properties of SBI-087 were evaluated in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). METHODS: Single-dose SBI-087 was evaluated in 2 Phase I, open-label, escalating-dose studies in patients with RA or SLE. The studies included 6 IV/4 SC escalating doses (RA) and 1 IV/4 SC escalating doses (SLE). Escalation was determined by tolerability/rate of B-cell depletion. Serum was collected for analyses of pharmacokinetic and pharmacodynamic (CD19(+) B cells) properties and immunogenicity. Patients were followed until B-cell counts were normalized or stabilized. Safety, tolerability was evaluated from adverse events, physical examinations, vital sign measurements, ECG, and clinical laboratory results. FINDINGS: Sixty patients with RA (IV, 28; SC, 32) and 30 patients with SLE (6 per cohort) were enrolled. Mild to moderate infusion reactions occurred in several patients at the top doses in the RA study despite a pretreatment regimen of IV doses. Unanticipated reactions after SC administration of SBI-087 included fever, chills, and malaise, seen on the day of dosing in the lowest-dose cohorts in both studies. These events were abrogated in subsequent cohorts by a pre/postdose treatment regimen consisting of oral corticosteroids, acetaminophen, and an antihistamine. SBI-087 clearance (IV) ranged from 22 to 229 mL/h; volume of distribution at steady state ranged from 5 to 12 L. Apparent clearance (SC) ranged from 44.7 to 105 mL/h; volume of distribution ranged from 14.3 to 32.1 L. Overall, PK properties were similar at equivalent doses between IV/SC administrations in patients with RA/SLE. Mean t½ (IV) ranged from 2.1 to 10.7 days (less at lower doses). SBI-087 concentration and B-cell depletion were generally dose proportional across IV and SC cohorts. However, the extent of B-cell depletion was less, and rate of repletion was faster, in patients with SLE versus RA. In both studies, B-cell repletion to baseline did not occur in the majority of patients by the end of the observation period. Overall, the prevalence and type of adverse events were similar to those seen with other anti-CD20-depleting agents. IMPLICATIONS: In patients with mild RA/SLE, SBI-087 was well tolerated when administered intravenously or subcutaneously with pre- and posttreatment regimens. B-cell depletion is long lasting, and the duration and extent of depletion may be greater in RA compared with SLE. SBI-087 exhibited slow elimination and low distribution in both populations. Clinicaltrials.gov identifiers: NCT00641225 (RA) and NCT00714116 (SLE).

7 Clinical Trial Long-Term Safety and Efficacy of Epratuzumab in the Treatment of Moderate-to- Severe Systemic Lupus Erythematosus: Results From an Open-Label Extension Study. 2016

Wallace, D J / Hobbs, K / Clowse, M E B / Petri, M / Strand, V / Pike, M / Merrill, J T / Leszczyński, P / Neuwelt, C M / Jeka, S / Houssiau, F / Keiserman, M / Ordi-Ros, J / Bongardt, S / Kilgallen, B / Galateanu, C / Kalunian, K / Furie, R / Gordon, C. ·Cedars-Sinai Medical Center, Los Angeles, California. · Denver Arthritis Clinic, Denver, Colorado. · Duke University Medical Center, Durham, North Carolina. · Johns Hopkins University School of Medicine, Baltimore, Maryland. · Biopharmaceutical Consultant, Portola Valley, California. · MedPharm Consulting, Inc., Cambridge, Massachusetts. · Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City. · Poznan University of Medical Sciences, Poznan, Poland. · Alameda County Health System, Oakland, California. · Clinic of Rheumatology and Connective Tissue Diseases, 2nd University Hospital, CM UMK, Bydgoszcz, Poland. · Clinique Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. · Pontifical Catholic University, School of Medicine, Porto Alegre, Brazil. · Universitari Vall d'Hebron, Barcelona, Spain. · UCB Pharma, Monheim, Germany. · UCB Pharma, Raleigh, North Carolina. · UCB Pharma, Brussels, Belgium. · University of California San Diego School of Medicine, La Jolla. · North Shore-Long Island Jewish Health System, New York, New York. · School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, and NIHR/Wellcome Trust Clinical Research Facility, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK. ·Arthritis Care Res (Hoboken) · Pubmed #26316325.

ABSTRACT: OBJECTIVE: The primary objective was to assess the long-term safety of repeated courses of epratuzumab therapy in patients with moderate-to-severe systemic lupus erythematosus. Secondary objectives were to assess long-term efficacy and health-related quality of life (HRQOL). METHODS: Eligible patients from the 12-week, phase IIb, randomized, placebo-controlled EMBLEM study enrolled into the open-label extension (OLE) study, SL0008. In the SL0008 study, patients received 1,200 mg epratuzumab infusions at weeks 0 and 2 of repeating 12-week cycles, plus standard of care. Safety measures included treatment-emergent adverse events (TEAEs) and serious TEAEs. Efficacy measures included combined treatment response, the British Isles Lupus Assessment Group score, the Systemic Lupus Erythematosus Disease Activity Index score, and the physician's and patient's global assessment of disease activity. Total daily corticosteroid dose and HRQOL (by the Short Form 36 health survey) were also assessed. RESULTS: A total of 113 of the 203 patients (55.7%) who entered the SL0008 study continued epratuzumab therapy until study closure (total cumulative exposure: 381.3 patient-years, median exposure: 845 days, and maximum exposure: 1,185 days/approximately 3.2 years). TEAEs were reported in 192 patients (94.6%); most common were infections and infestations (68.0%, 138 patients). Serious TEAEs were reported in 51 patients (25.1%), and 14 patients (6.9%) had serious infections. In patients treated for 108 weeks (n = 116), the median corticosteroid dose was reduced from 10.0 mg/day at OLE screening to 5.0 mg/day at week 108. Improvements in efficacy and HRQOL measures in EMBLEM were maintained in the OLE, while placebo patients exhibited similar improvements in disease activity upon a switch to epratuzumab. CONCLUSION: Open-label epratuzumab treatment was well tolerated for up to 3.2 years, and associated with sustained improvements in disease activity and HRQOL, while steroids were reduced.

8 Article Provider perceptions on the management of lupus during pregnancy: barriers to improved care. 2019

Clowse, M E B / Eudy, A M / Revels, J / Neil, L / Sanders, G D. ·1 Division of Rheumatology & Immunology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. · 2 Duke Office of Clinical Research, Duke University School of Medicine, Durham, North Carolina, USA. · 3 Department of Population Health Sciences, Duke University School of Medicine, Durham, North Carolina, USA; Duke Clinical Research Institute, Duke University, Durham, North Carolina, USA; Duke-Margolis Center for Health Policy, Duke University, Durham, North Carolina, USA. ·Lupus · Pubmed #30522398.

ABSTRACT: BACKGROUND: More than half of pregnancies in women with systemic lupus erythematosus (lupus) result in adverse outcomes for the mother or the fetus. We sought to identify aspects of current rheumatologic care that could be improved to decrease the frequency of poor outcomes. METHODS: Focus groups with clinical rheumatologists, based on the PRECEDE/PROCEED framework, identified factors that influenced care. A group of women with lupus on their reproductive journey contributed to our understanding of the dilemmas and care provided. RESULTS: Medically ill-timed pregnancies and medication non-adherence during pregnancy were identified by rheumatologists as the two key dilemmas in care. We identified several communication gaps as key modifiable barriers to optimal management. The approach to physician-patient communication was often unsuitable to sensitive discussions about pregnancy planning. The communication of treatment plans was frequently hampered by gaps in knowledge and both physician and patient confidence in the data, encouraging non-adherence among nervous patients. Finally, local rheumatologists and obstetricians/gynecologists providers frequently did not communicate, leading to varying treatment plans and confusion for patients. CONCLUSIONS: To decrease the frequency of ill-timed pregnancy and medication non-adherence it will be essential to empower rheumatologists, and women with lupus to have open and accurate conversations about pregnancy planning and management.

9 Article Power in numbers. 2018

Vinet, Evelyne / Chakravarty, Eliza F / Clowse, Megan E B. ·Divisions of Clinical Epidemiology and Rheumatology, McGill University Health Centre, Montreal, Québec, Canada. · Division of Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK. · Division of Rheumatology, Duke University Medical Center, Durham, NC, USA. ·Rheumatology (Oxford) · Pubmed #30137590.

ABSTRACT: Collecting useful data on a sufficiently large cohort of pregnancies in women with rheumatic disease is a challenge. The original manuscripts that demonstrated the dangers of pregnancy in women with lupus were relatively small case series. As larger prospective cohorts were collected by university-based experts, however, greater safety was demonstrated and the current norms of treatment were determined. In recent years, larger administrative databases have been tapped to study pregnancies not managed within university clinics and to study the long-term impact of maternal rheumatic disease on the offspring. Each of these methods of study has both strengths and weaknesses, adding a unique piece of data to our overall knowledge. We will discuss a range of approaches to the study of rheumatic disease in pregnancy, covering the potential benefits that each brings as well as the biases that can impact study results. When the results of studies are viewed through these lenses, each can contribute to our larger understanding of the rheumatic diseases in pregnancy.

10 Article The prevention, screening and treatment of congenital heart block from neonatal lupus: a survey of provider practices. 2018

Clowse, Megan E B / Eudy, Amanda M / Kiernan, Elizabeth / Williams, Matthew R / Bermas, Bonnie / Chakravarty, Eliza / Sammaritano, Lisa R / Chambers, Christina D / Buyon, Jill. ·Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC. · Department of Pediatrics, Division of Dysmorphology and Teratology, University of California San Diego, San Diego, CA. · Pediatric Cardiology and Cardiovascular Surgery, Rady Children's Hospital, University of California San Diego, San Diego, CA. · Division of Rheumatic Diseases, UT Southwestern, Dallas, TX. · Department of Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK. · Division of Rheumatology, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY. · Department of Pediatrics, University of California San Diego, San Diego, CA. · Division of Rheumatology, New York University School of Medicine, NY, USA. ·Rheumatology (Oxford) · Pubmed #30137589.

ABSTRACT: Objective: To survey an international sample of providers to determine their current practices for the prevention, screening, and treatment of congenital heart block (CHB) due to maternal Ro/SSA antibodies. Methods: A survey was designed by the organizing committee of the 9th International Conference of Reproduction, Pregnancy and Rheumatic Diseases. It was sent to attendants of the conference and authors of recent publications or abstracts at ACR 2012, 2013 or 2014 on rheumatic diseases and pregnancy. Results: In anti-Ro/SSA positive women, 80% of 49 respondents recommended screening by serial fetal echocardiogram (ECHO), with most starting at week 16 (59%) and stopping at week 28 (25%), although the time to stop varied widely. For women without a prior infant with neonatal lupus, respondents recommend every other week (44%) or weekly (28%) fetal ECHOs. For women with a prior infant with neonatal lupus, 80% recommend weekly fetal ECHOs. To prevent CHB, HCQ was recommended by 67% of respondents and most would start pre-pregnancy (62%). Respondents were asked about medications to treat varying degrees of CHB in a 20-week pregnant, anti-Ro and La positive SLE patient. For first degree, respondents recommended starting dexamethasone (53%) or HCQ (43%). For second degree, respondents recommended starting dexamethasone (88%). For third degree, respondents recommended starting dexamethasone (55%) or IVIg (33%), although 27% would not start treatment. Conclusion: Despite the absence of official guidelines, many physicians with a focus on pregnancy and rheumatic disease have developed similar patterns in the screening, prevention and treatment of CHB.

11 Article Reasons for cesarean and medically indicated deliveries in pregnancies in women with systemic lupus erythematosus. 2018

Eudy, A M / Jayasundara, M / Haroun, T / Neil, L / James, A H / Clowse, M E B. ·Duke University Medical Center, Durham, NC, USA. ·Lupus · Pubmed #28699378.

ABSTRACT: Objective To determine reasons for cesarean and medically indicated deliveries in a registry of pregnant women with SLE compared to RA. Methods Pregnant women with SLE or RA were prospectively followed, and pregnancy outcomes were collected, including whether labor was spontaneous or medically indicated and delivery was vaginal or cesarean. Preterm birth was defined as a birth <37 weeks gestation. Differences in reasons for cesarean delivery and indication of delivery between term and preterm births were determined by Fisher's exact test. Results Compared to RA pregnancies, SLE pregnancies had modestly higher rates of preterm birth (24% SLE vs 14% RA), pre-eclampsia (15% SLE vs 7% RA), and cesarean delivery (48% SLE vs 30% RA). The majority of preterm births among women with SLE were indicated (70%), most commonly for pre-eclampsia or the health of the infant or mother. The majority of preterm births among women with RA, however, were spontaneous, primarily due to premature rupture of membranes. Conclusion Pre-eclampsia and maternal SLE activity appear to be the key drivers for the high rate of preterm birth and medically indicated delivery in SLE. This contrasts with RA, where preterm labor is most often due to spontaneous onset of labor.

12 Article Examination of Hydroxychloroquine Use and Hemolytic Anemia in G6PDH-Deficient Patients. 2018

Mohammad, Samya / Clowse, Megan E B / Eudy, Amanda M / Criscione-Schreiber, Lisa G. ·Duke University Medical Center, Durham, North Carolina. ·Arthritis Care Res (Hoboken) · Pubmed #28556555.

ABSTRACT: OBJECTIVE: Some sources urge caution when prescribing hydroxychloroquine (HCQ) to patients with G6PDH deficiency, presumably due to a risk of hemolytic anemia. There are limited published data, however, to support this risk. Additionally, not all patients with G6PDH deficiency are at similar risk for hemolysis, and people with the African variant are at particularly low risk. Through a retrospective chart review, we aimed to quantify the frequency of G6PDH-deficient patients with hemolysis attributed to HCQ. METHODS: We identified Duke University Medical Center rheumatology patients with HCQ use and a measured G6PDH level. A retrospective chart review was performed, recording demographics, G6PDH levels, episodes of anemia, laboratory values consistent with hemolysis, and HCQ use. RESULTS: Of the 275 patients reviewed, 84% were female; 46% were African American and 48% were white. The leading diagnoses were systemic lupus erythematosus (32%), rheumatoid arthritis (29%), and inflammatory arthritis (14%). Only 4% of patients were G6PDH deficient (all African American). Two G6PDH-deficient patients had hemolysis during severe lupus flares that occurred while not taking HCQ. There were no reported episodes of hemolysis in more than 700 months of HCQ exposure among the 11 G6PDH-deficient patients. CONCLUSION: This is the largest study to date evaluating G6PDH deficiency with concurrent use of HCQ. Of 11 patients with G6PDH deficiency, 2 had episodes of hemolysis, but these did not occur during HCQ therapy. These data do not support routine measurement of G6PDH levels or withholding HCQ therapy among African American patients with G6PDH deficiency.

13 Article Gestational weight gain in women with systemic lupus erythematosus. 2017

Eudy, A M / Siega-Riz, A M / Engel, S M / Franceschini, N / Howard, A G / Clowse, M E B / Petri, M. ·1 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina Chapel Hill, Chapel Hill, USA. · 2 Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina Chapel Hill, Chapel Hill, USA. · 3 Division of Rheumatology & Immunology, Duke University Medical Center, Durham, USA. · 4 Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, USA. ·Lupus · Pubmed #27703053.

ABSTRACT: Objective The objective of this study was to estimate the proportion of pregnant women with systemic lupus erythematosus meeting Institute of Medicine guidelines for gestational weight gain and determine correlates of adherence to guidelines. Methods Singleton, live births in the Hopkins Lupus Pregnancy Cohort 1987-2015 were included. Pre-pregnancy weight was the weight recorded 12 months prior to pregnancy/first trimester. Final weight was the last weight recorded in the third trimester. Adherence to Institute of Medicine guidelines (inadequate, adequate, or excessive) was based on pre-pregnancy body mass index. Fisher's exact test and analysis of variance determined factors associated with not meeting guidelines. Stepwise selection estimated predictors of gestational weight gain. Results Of the 211 pregnancies, 34%, 24% and 42% had inadequate, adequate and excessive gestational weight gain, respectively. In exploratory analyses, differences in Institute of Medicine adherence were observed by pre-pregnancy body mass index, race, elevated creatinine during pregnancy and pre-pregnancy blood pressure. Odds of inadequate and excessive gestational weight gain increased 12% with each 1 kg/m

14 Article Breastfeeding in mothers with systemic lupus erythematosus. 2016

Noviani, M / Wasserman, S / Clowse, M E B. ·Department of Rheumatology, Duke University Medical Center, Durham, NC, USA Duke-National University of Singapore Graduate Medical School, Singapore. · Department of Rheumatology, Duke University Medical Center, Durham, NC, USA. · Department of Rheumatology, Duke University Medical Center, Durham, NC, USA megan.clowse@duke.edu. ·Lupus · Pubmed #26888577.

ABSTRACT: INTRODUCTION: Breastfeeding is known to improve the well-being of a mother and her infant, and about half of all new mothers breastfeed, but it is unknown how breastfeeding is pursued in systemic lupus erythematosus (SLE; lupus) patients. We sought to determine the rate of breastfeeding and the factors influencing this among women with lupus. In addition, we reassessed the current safety data in lactation of lupus medications. METHODS: Data were collected from lupus patients enrolled in a prospective registry who fulfilled the 2012 SLICC criteria, had a live birth, and for whom postpartum breastfeeding status was known. Data included physician assessments of lupus activity and medications, breastfeeding intentions during pregnancy and practice following pregnancy. The safety of medications in breastfed infants was assessed through a comprehensive review of LactMed, a national database about medications in lactation. RESULTS: A total of 51 pregnancies in 84 women with lupus were included in the study. Half of the lupus patients (n = 25, 49%) chose to breastfeed. The rate of breastfeeding was not significantly affected by socioeconomic factors. In contrast, low postpartum lupus activity, term delivery, and a plan to breastfeed early in pregnancy were significantly associated with breastfeeding in lupus patients. In reviewing the most up-to-date data, the majority of lupus medications appear to have very minimal transfer into breast milk and are likely compatible with breastfeeding. CONCLUSION: Half of women with lupus breastfed and most desire to breastfeed. Hydroxychloroquine, azathioprine, methotrexate, and prednisone have very limited transfer into breast milk and may be continued while breastfeeding.

15 Article Racial and Ethnic Disparities in the Pregnancies of Women With Systemic Lupus Erythematosus. 2016

Clowse, Megan E B / Grotegut, Chad. ·Duke University, Durham, North Carolina. megan.clowse@duke.edu. · Duke University, Durham, North Carolina. ·Arthritis Care Res (Hoboken) · Pubmed #26815791.

ABSTRACT: OBJECTIVE: Both systemic lupus erythematosus (SLE; lupus) and pregnancy individually have significant racial disparities, with black women experiencing higher rates of complications, yet no large studies have focused on the impact of race/ethnicity on pregnancy outcomes among women with lupus. METHODS: Using the Nationwide Inpatient Sample (NIS) for 2008-2010, pregnancy delivery discharges were identified and pregnancy outcomes were compared for women with lupus by maternal race/ethnicity. Adjusted odds ratios were used to compare pregnancy outcomes between black and white or Hispanic and white women with lupus. RESULTS: In this period, the NIS included 13,553 deliveries with lupus and 12,510,565 deliveries without lupus. Compared to white women with lupus, black and Hispanic women had higher rates of chronic hypertension, chronic renal failure, pneumonia, and acute renal failure. There was a high degree of pregnancy complication in all women with lupus, but especially in black and Hispanic women, with more than 40% cesarean-section delivery; preterm labor in 14.3% of white, 24.7% of black (odds ratio [OR] 1.97), and 20.6% of Hispanic (OR 1.56) deliveries; and preeclampsia and gestational hypertension in almost 20% of black and Hispanic pregnancies. After adjustment for predictors of pregnancy outcomes and racial differences in nonlupus pregnancy, black and Hispanic women with lupus had higher than expected rates of preeclampsia, preterm labor, and fetal growth restriction. CONCLUSION: Black and Hispanic women with lupus have disproportionately poor pregnancy outcomes. This study suggests that identifying the key causes of these differences and targeting interventions to the women of greatest need is an essential next step.

16 Article Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus. 2015

Aranow, Cynthia / Kamen, Diane L / Dall'Era, Maria / Massarotti, Elena M / Mackay, Meggan C / Koumpouras, Fotios / Coca, Andreea / Chatham, W Winn / Clowse, Megan E B / Criscione-Schreiber, Lisa G / Callahan, Sherri / Goldmuntz, Ellen A / Keyes-Elstein, Lynette / Oswald, Michaela / Gregersen, Peter K / Diamond, Betty. ·Feinstein Institute for Medical Research, Manhasset, New York. · Medical University of South Carolina, Charleston. · University of California, San Francisco. · Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. · West Penn Hospital, Pittsburgh, Pennsylvania. · University of Rochester, Rochester, New York. · University of Alabama at Birmingham. · Duke University Medical Center, Durham, North Carolina. · National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland. · Rho Federal Systems, Chapel Hill, North Carolina. ·Arthritis Rheumatol · Pubmed #25777546.

ABSTRACT: OBJECTIVE: Vitamin D modulates the immune response and blocks induction of an interferon (IFN) signature by systemic lupus erythematosus (SLE) sera. This study was undertaken to investigate the effects of vitamin D supplementation on the IFN signature in patients with SLE. METHODS: SLE patients (n = 57) with stable, inactive disease, a serum 25-hydroxyvitamin D (25[OH]D) level ≤20 ng/ml, an elevated anti-double-stranded DNA antibody level, and an IFN signature (as determined by measuring the expression levels of 3 IFN response genes) were randomized into a 12-week double-blind, placebo-controlled trial of vitamin D3 at doses of 2,000 IU or 4,000 IU. An IFN signature response was defined as a 50% reduction in the expression of 1 of the 3 genes or a 25% reduction in the expression of 2 of the 3 genes. Disease activity, adverse events, and endocrine effects were assessed. RESULTS: Baseline characteristics of the patients in the 3 treatment groups (placebo, low-dose vitamin D3 , or high-dose vitamin D3 ) were similar. Repletion of 25(OH)D (i.e., levels ≥30 ng/ml) was not observed in any of the patients who were receiving placebo, while repletion was observed in 16 of 33 patients receiving vitamin D3 . The percentage of patients with an IFN signature response did not differ among the treatment groups. Moreover, there was no difference in the percentage of patients with an IFN signature response between those who remained vitamin D deficient and those who demonstrated repletion of vitamin D. Modular microarray analysis of a subset of patients (n = 40) did not reveal changes from baseline in any modules (including the IFN-inducible module) in any of the treatment groups, and no differences in expression were found between patients who demonstrated vitamin D repletion and patients who were persistently vitamin D deficient. Vitamin D3 was well tolerated, and there were no safety concerns. CONCLUSION: Vitamin D3 supplementation up to 4,000 IU daily was safe and well-tolerated but failed to diminish the IFN signature in vitamin D-deficient SLE patients. Higher 25(OH)D levels sustained for a longer duration may be required to affect immunologic outcomes.

17 Article An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1. 2014

Bonsignori, Mattia / Wiehe, Kevin / Grimm, Sebastian K / Lynch, Rebecca / Yang, Guang / Kozink, Daniel M / Perrin, Florence / Cooper, Abby J / Hwang, Kwan-Ki / Chen, Xi / Liu, Mengfei / McKee, Krisha / Parks, Robert J / Eudailey, Joshua / Wang, Minyue / Clowse, Megan / Criscione-Schreiber, Lisa G / Moody, M Anthony / Ackerman, Margaret E / Boyd, Scott D / Gao, Feng / Kelsoe, Garnett / Verkoczy, Laurent / Tomaras, Georgia D / Liao, Hua-Xin / Kepler, Thomas B / Montefiori, David C / Mascola, John R / Haynes, Barton F. · ·J Clin Invest · Pubmed #24614107.

ABSTRACT: Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1-infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1-infected individual with SLE who exhibited controlled viral load (<5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient's plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells.

18 Article Predictors of preterm birth in patients with mild systemic lupus erythematosus. 2013

Clowse, Megan E B / Wallace, Daniel J / Weisman, Michael / James, Andra / Criscione-Schreiber, Lisa G / Pisetsky, David S. ·Department of Medicine, Duke University Medical Center, , Durham, NC 27710, USA. megan.clowse@duke.edu ·Ann Rheum Dis · Pubmed #23361085.

ABSTRACT: OBJECTIVE: While increased disease activity is the best predictor of preterm birth in women with systemic lupus erythematosus (SLE), even women with low disease activity are at increased risk of this complication. Biomarkers that would identify at-risk pregnancies could allow interventions to prevent preterm birth. METHOD: Measures of SLE activity, inflammation, placental health and renal function between 20 and 28 weeks gestation (mid-gestation) were correlated to preterm birth and gestational age at delivery in a prospective cohort of pregnant women with SLE. RESULT: Of the 40 pregnancies in 39 women, all with mild-moderate SLE disease, 9 (23.7%) of the 38 live births were delivered preterm. Low C4 was the only marker of SLE activity associated with younger gestational age at delivery. Elevated ferritin and lower oestradiol correlated with younger gestational age at delivery. Renal function remained normal during all pregnancies at mid-gestation and did not correlate with preterm birth. Higher serum uric acid, however, correlated with younger gestational age at delivery. CONCLUSIONS: In women with SLE with mild-moderate disease activity, ferritin, oestradiol and uric acid levels at mid-gestation may predict preterm birth. These markers may prove to be clinically useful in identifying pregnancies at particularly high risk for adverse outcomes.

19 Article Depressive symptoms and associated factors in systemic lupus erythematosus. 2013

Karol, David E / Criscione-Schreiber, Lisa G / Lin, Min / Clowse, Megan E B. ·Duke University Medical Center, Durham, NC. ·Psychosomatics · Pubmed #23274009.

ABSTRACT: BACKGROUND: Depressive symptoms affect anywhere from 11% to 71% of patients with systemic lupus erythematosus (SLE), which may be related to SLE disease activity, other clinical variables, or sociodemographic factors. OBJECTIVE: We aimed to measure the rate of depressive symptoms in our cohort of patients with SLE and to identify modifiable factors associated with depressive symptoms. METHODS: Patients in our university-based SLE registry completed the Beck Depression Inventory-II (BDI-II), pain scores, and demographic information. Disease activity was measured using the physician's global assessment (PGA) and Selena-SLE disease activity index (Selena-systemic lupus erythematosus disease activity index (SLEDAI)). Patients were identified as having moderate or severe depressive symptoms (BDI-II ≥ 18) or not (BDI-II < 18). Nonparametric tests and χ(2) tests were used as appropriate to compare variables between groups. RESULTS: Fifty-three of 127 people (41.7%) were identified as having moderate or severe depressive symptoms, which were associated with higher pain levels and lower self-reported of current health status. Patients with moderate or severe depressive symptoms were more likely (49%) than those with no or mild depressive symptoms (18%) to have lupus arthritis (P < 0.01). Of the 53 patients with moderate or severe depressive symptoms, only 26 (49.0%) were prescribed antidepressants, and only 8/53 patients (15.0%) were prescribed the maximum dose of antidepressant. CONCLUSIONS: This study identified moderate or severe depressive symptoms in 41.7% of our cohort of patients with SLE. The most significant variable associated with these symptoms was pain; improved treatment of pain, and in particular from lupus arthritis, may result in alleviation of depressive symptoms in patients with SLE.

20 Article The impact of cyclophosphamide on menstruation and pregnancy in women with rheumatologic disease. 2013

Harward, L E / Mitchell, K / Pieper, C / Copland, S / Criscione-Schreiber, L G / Clowse, M E B. ·Department of Medicine, Medical University of South Carolina, USA. ·Lupus · Pubmed #23263867.

ABSTRACT: BACKGROUND: While cyclophosphamide (CYC) can save the life of a young woman with severe rheumatologic disease, it may lead to the long-term side-effects of infertility and premature menopause. We compared the reproductive health histories of young women with rheumatologic disease with and without prior CYC exposure to identify the impact of this medication on this important component of health. METHODS: This research includes a case-series study of women diagnosed with SLE, vasculitis, and scleroderma prior to age 35. Each patient completed a questionnaire about desired childbearing, menstrual regularity, infertility, and pregnancy history. Women with prior CYC therapy were queried about the use of gonadotropin-releasing hormone agonists (GnRH-a) for fertility preservation. The responses to this questionnaire were compared for women with and without CYC exposure. RESULTS: Of the 43 participants, 23 had prior CYC exposure and 20 were CYC naïve. The current age of these groups was similar (average age 32), but women with prior CYC were four years younger at diagnosis than women without CYC. More women with prior CYC had cessation of menses in the year prior to the study (30.4% vs 0%, p < 0.05). Of the women with prior CYC exposure, those with loss of menses were older at study enrollment, older at CYC treatment, and had a higher cumulative CYC dose than those with preserved menstruation. While more women with GnRH-a co-therapy during CYC had maintained menses, this difference did not reach statistical significance. Women with prior CYC without GnRH-a co-therapy had a higher frequency of nulliparity and had greater trouble conceiving than women with GnRH-a co-therapy. Few pregnancies were conceived following CYC exposure and all resulted in elective termination, miscarriage, or preterm birth. CONCLUSION: In this cohort of young women with rheumatologic disease, more women with prior CYC than without had amenorrhea, nulliparity, and infertility. GnRH-a co-therapy may prevent these adverse effects of CYC.

21 Article Self-efficacy and pain catastrophizing in systemic lupus erythematosus: relationship to pain, stiffness, fatigue, and psychological distress. 2012

Somers, Tamara J / Kurakula, Preethi C / Criscione-Schreiber, Lisa / Keefe, Francis J / Clowse, Megan E B. ·Duke University Medical Center, Durham, North Carolina, USA. tamara.somers@duke.edu ·Arthritis Care Res (Hoboken) · Pubmed #22505314.

ABSTRACT: OBJECTIVE: To determine how self-efficacy for pain control and pain catastrophizing, both potentially modifiable pain coping cognitions, are related to pain, stiffness, fatigue, and psychological distress in patients with systemic lupus erythematosus (SLE). METHODS: We conducted a cross-sectional study of patients with SLE who completed measures of pain coping cognitions (i.e., self-efficacy for pain control, pain catastrophizing), symptom ratings (i.e., pain, stiffness, fatigue), and psychological distress. RESULTS: Correlational analyses revealed that self-efficacy for pain control and pain catastrophizing were associated with the patients' physical symptom reports and psychological distress. After controlling for age, race, and disease activity, patients with lower levels of self-efficacy for pain control reported much higher levels of pain, stiffness, and fatigue. Patients with higher levels of pain catastrophizing reported much lower positive mood. SLE activity as assessed by the rheumatologist was not associated with physical symptoms, psychological distress, self-efficacy for pain control, or pain catastrophizing. CONCLUSION: These results suggest that pain coping cognitions (i.e., either self-efficacy for pain control or pain catastrophizing) are significantly related to physical symptoms and psychological distress in patients with SLE. This finding is important because the results of studies from other samples of patients with persistent pain conditions have shown that these pain coping variables can be modified using psychological interventions, and that such treatment-related changes in pain cognitions are related to improved patient outcomes.

22 Article Effects of infertility, pregnancy loss, and patient concerns on family size of women with rheumatoid arthritis and systemic lupus erythematosus. 2012

Clowse, Megan E B / Chakravarty, Eliza / Costenbader, Karen H / Chambers, Christina / Michaud, Kaleb. ·Duke University Medical Center, Durham, North Carolina, USA. ·Arthritis Care Res (Hoboken) · Pubmed #22344961.

ABSTRACT: OBJECTIVE: Women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have fewer children on average than other women. We sought to determine the roles of infertility, pregnancy loss, and personal choice on family size in women with these diseases. METHODS: A reproductive history questionnaire was completed by women with RA and SLE participating in a longitudinal observational study. Within each disease cohort, participants were divided into 3 groups: those interested in having children at symptom onset who had either fewer children than planned (group A) or the same number as planned (group B), and those no longer interested in having children at diagnosis (group C). RESULTS: Of the 578 RA and 114 SLE women surveyed, >60% were in group C. Of those interested in having children, 55% with RA and 64% with SLE had fewer children than originally planned. Among women with RA, group A had 1 less pregnancy, 1 less live birth, and an infertility rate 1.5 times higher than group B; the miscarriage rate was similar in both groups. Compared to SLE group B, SLE group A had a similar number of pregnancies, but a 3-fold higher rate of miscarriage and 1 less live birth. Concerns about child health and personal welfare were associated with a lower pregnancy rate. CONCLUSION: In this population, more than one-half of young women with RA or SLE had fewer biologic children than desired. While patient choice plays a role, infertility in RA patients and miscarriage in SLE patients are also important.

23 Article The clinical utility of measuring complement and anti-dsDNA antibodies during pregnancy in patients with systemic lupus erythematosus. 2011

Clowse, Megan E B / Magder, Laurence S / Petri, Michelle. ·Division of Rheumatology, Duke University Medical Center, Durham, North Carolina, USA. megan.clowse@duke.edu ·J Rheumatol · Pubmed #21406496.

ABSTRACT: OBJECTIVE: The importance of low complement and anti-dsDNA during pregnancy in patients with systemic lupus erythematosus (SLE) is poorly defined. We investigated the effect of these laboratory tests and clinical SLE activity on pregnancy outcomes. METHODS: We conducted a study of all pregnancies in patients with SLE followed from 1986 to 2002 in a cohort of patients with SLE. At each visit, the physician's estimate of activity (PEA), complement, and anti-dsDNA antibody were measured. We assessed the combination of moderate to severe SLE clinical activity (defined as PEA ≥ 2) and these serologic measurements on pregnancy outcomes. Pregnancies electively terminated were excluded from our study. RESULTS: Regardless of SLE activity, low complement or positive anti-dsDNA in the second trimester was associated with a higher rate of pregnancy loss and preterm birth. Patients with the combination of either high clinical activity of SLE and low complement or positive anti-dsDNA had the highest rate of pregnancy loss and preterm birth. CONCLUSION: Women with the combination of high clinical activity with serologic markers of SLE activity are at highest risk for pregnancy loss and preterm delivery. While hypocomplementemia and positive anti-dsDNA alone are predictive of poor pregnancy outcomes in the second trimester, the risks are far higher for the women in whom this is coupled with clinically active SLE.

24 Article Microparticles as antigenic targets of antibodies to DNA and nucleosomes in systemic lupus erythematosus. 2011

Ullal, Anirudh J / Reich, Charles F / Clowse, Megan / Criscione-Schreiber, Lisa G / Tochacek, Martin / Monestier, Marc / Pisetsky, David S. ·Duke University Medical Center, Department of Medicine, Durham, NC 27705, USA. ·J Autoimmun · Pubmed #21376534.

ABSTRACT: Systemic lupus erythematosus is a prototypic autoimmune disease characterized by antibodies to DNA and other nuclear molecules. While these antibodies can form immune complexes, the mechanisms generating the bound nuclear antigens are not known. These studies investigated whether microparticles can form complexes with anti-DNA and other anti-nucleosomal antibodies. Microparticles are small membrane-bound vesicles released from dead and dying cells; these particles contain a variety of cellular components, including DNA. To assess antigenicity, microparticles generated in vitro from apoptotic cell lines were tested using murine monoclonal anti-DNA and anti-nucleosomal antibodies as well as plasma from lupus patients. Antibody binding was assessed by flow cytometry. As these studies showed, some but not all of the monoclonal antibodies bound to microparticles prepared from apoptotic HL-60, THP-1 and Jurkat cells. For HL-60 cells, both staurosporine and UV radiation led to the production of antigenically active particles. For the anti-DNA antibody with high particle binding, prior treatment of DNase reduced activity. With plasma from patients with SLE, antibody binding to microparticles was present although a clear relationship with anti-DNA antibody levels was not observed. To determine whether lupus plasma contains immune complexes with particle properties, particle preparations were tested for bound IgG by flow cytometry. These studies indicated that lupus plasma contains particles with IgG binding, with numbers correlated with anti-DNA levels. Together, these findings indicate that microparticles display DNA and nucleosomal molecules in an antigenic form and could represent a source of immune complexes in SLE.

25 Article Late ovarian hyperstimulation syndrome after controlled ovarian stimulation in a woman with systemic lupus erythematosus and lupus nephritis. 2011

Crochet, John R / Yeh, Jason S / Clowse, Megan E B / Copland, Susannah D. ·Division of Reproductive Endocrinology and Fertility, Department of Obstetrics and Gynecology, Duke University Hospital, Durham, North Carolina, USA. john.crochet@duke.edu ·Fertil Steril · Pubmed #21168129.

ABSTRACT: OBJECTIVE: To report a case of late ovarian hyperstimulation syndrome (OHSS) in a woman with lupus nephritis undergoing controlled ovarian stimulation and in vitro fertilization (IVF) with subsequent transfer into a gestational surrogate. DESIGN: A case report. SETTING: Academic reproductive medicine clinic. PATIENT(S): A 33-year-old woman who presented 10 days after recombinant human chorionic gonadotropin (hCG) injection with fatigue, abdominal pain, and bloating, diagnosed as OHSS. INTERVENTION(S): Patient admitted for intravenous fluid hydration, anticoagulation, and gonadotropin-releasing hormone (GnRH) antagonist therapy. MAIN OUTCOME MEASURE(S): Successful detection and management of severe OHSS in a patient with chronically impaired kidney function. RESULT(S): The patient has returned to her baseline condition, and the gestational carrier was noted to have a twin gestation. CONCLUSION(S): In patients with impaired renal function, final oocyte maturation should be triggered with a GnRH agonist rather than hCG.

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