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      Complement Activation in Patients With Probable Systemic Lupus Erythematosus and Ability to Predict Progression to American College of Rheumatology–Classified Systemic Lupus Erythematosus

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          Abstract

          Objective

          To evaluate the frequency of cell‐bound complement activation products ( CBCAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus ( SLE) and the usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology ( ACR) criteria.

          Methods

          Patients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics ( SLICC) criteria, patients with primary Sjögren's syndrome ( SS), and patients with other rheumatic diseases. Individual CBCAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel ( MAP), which includes CBCAPs, was also evaluated. Probable SLE cases were followed up prospectively.

          Results

          The 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CBCAPs (28%) or MAP (40%) than had low complement levels (9%) ( P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01).

          Conclusion

          Complement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CBCAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria.

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          Most cited references37

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            Combined oral contraceptives in women with systemic lupus erythematosus.

            Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus. A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 microg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial). Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable. Copyright 2005 Massachusetts Medical Society.
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              Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort

              Background and aims We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients. Methods The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan–Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality. Results We recruited 1722 patients; mean (SD) age 35.0 (13.4) years at cohort entry. Patients with damage at enrolment were more likely to have further worsening of SDI (SDI 0 vs ≥1; p<0.001). Age, USA African race/ethnicity, SLEDAI-2K score, steroid use and hypertension were associated with transition from no damage to damage, and increase(s) in pre-existing damage. Male gender (relative transition rates (95% CI) 1.48 (1.06 to 2.08)) and USA Caucasian race/ethnicity (1.63 (1.08 to 2.47)) were associated with SDI 0 to ≥1 transitions; Asian race/ethnicity patients had lower rates of new damage (0.60 (0.39 to 0.93)). Antimalarial use was associated with lower rates of increases in pre-existing damage (0.63 (0.44 to 0.89)). Damage was associated with future mortality (HR (95% CI) 1.46 (1.18 to 1.81) per SDI point). Conclusions Damage in SLE predicts future damage accrual and mortality. We identified several potentially modifiable risk factors for damage accrual; an integrated strategy to address these may improve long-term outcomes.
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                Author and article information

                Contributors
                aw89@georgetown.edu
                Journal
                Arthritis Rheumatol
                10.1002/(ISSN)2326-5205
                ART
                Arthritis & Rheumatology (Hoboken, N.j.)
                John Wiley and Sons Inc. (Hoboken )
                2326-5191
                2326-5205
                25 November 2019
                January 2020
                : 72
                : 1 ( doiID: 10.1002/art.v72.1 )
                : 78-88
                Affiliations
                [ 1 ] Northwestern University Feinberg School of Medicine Chicago Illinois
                [ 2 ] University of California San Diego
                [ 3 ] Exagen, Inc., Vista, California, and Georgetown University Washington DC
                [ 4 ] Exagen, Inc. Vista California
                [ 5 ] Brigham and Women’s Hospital Boston Massachusetts
                [ 6 ] Cedars Sinai Medical Center Los Angeles California
                [ 7 ] Northwell Health and Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Hempstead New York
                [ 8 ] Oklahoma Medical Research Foundation Oklahoma City
                [ 9 ] MedStar Washington Hospital Center Washington DC
                [ 10 ] New York University School of Medicine New York
                [ 11 ] Albert Einstein College of Medicine and Montefiore Medical Center New York New York
                Author notes
                [*] [* ]Address correspondence to Arthur Weinstein, MD, FACP, FRCP, MACR, 1261 Liberty Way, Vista, CA 92081. E‐mail: aw89@ 123456georgetown.edu .
                Author information
                https://orcid.org/0000-0002-9546-1664
                https://orcid.org/0000-0002-7248-6623
                Article
                ART41093
                10.1002/art.41093
                6972605
                31469249
                a9f6f9d0-8bfa-4906-a083-ca3da3f7b2b6
                © 2019, The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 14 June 2019
                : 27 August 2019
                Page count
                Figures: 3, Tables: 3, Pages: 11, Words: 8570
                Funding
                Funded by: Exagen, Inc
                Categories
                Original Article
                Systemic Lupus Erythematosus
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:21.01.2020

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