Session Information
Date: Sunday, November 5, 2017
Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment Poster I: Biomarkers and Outcomes
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: We sought to evaluate the relationships between low complement C3 and C4 proteins, abnormal complement activation (cell-bound complement activation products [CB-CAPs]), and a Lupus Severity Index (LSI) instrument recently developed.
Methods: The study was multi-centered and enrolled 500 SLE subjects (mean age 41.0±0.6 [SEM] years; 91% female; mean disease duration 10.9±0.4 years), all fulfilling the 1982 American College of Rheumatology (ACR) criteria revised in 1997. LSI was determined using the ACR criteria and sub-criteria elements collected from medical records as described (Bello et al., Lupus Science & Medicine 2016;3:e000136). Serum C3 and C4 levels were determined using standard immunochemistry techniques. Complement activation was assessed by quantitative flow cytometry, and abnormal activation was defined as levels of C4d bound to erythrocyte (EC4d) or B-lymphocytes (BC4d) above the 99th percentile of a control group of normal healthy individuals (>14 and >60 net mean fluorescence intensity [MFI], respectively). Multivariate linear regression analysis was used to evaluate the contributions of low complement and abnormal CB-CAPs to LSI, with age and disease duration as covariates. Pearson’s Chi-Square and Kruskal Wallis ANOVA tests were used as appropriate for group comparisons.
Results: In this cohort, median LSI score was 0.596 points (range 0.327-0.938 points, first tertile: 0.544; second tertile: 0.792). Multivariate linear regression analysis revealed that higher LSI scores were associated with abnormal CB-CAPs (estimate=0.063±0.015 points; p<0.01), low complement (estimate=0.030±0.015; p=0.048), younger age (estimate=-0.026±0.001 per 10-years increment; p<0.01), and longer disease duration (estimate=0.027±0.003 per 10-years increment, p<0.01) (Global R2=0.13). Altogether, subjects presenting with both low complement and abnormal CB-CAPs had higher LSI (median [IQ range]: 0.785 [0.558-0.839]) than those presenting with either abnormality (median [IQ range]: 0.591 [0.526-0.817]) or those presenting with normal complement and normal CB-CAPs (median [IQ range]: 0.546 [0.481-0.703]) (p<0.001). Figure 1 illustrates the higher frequencies of low complement (p<0.01) and abnormal CB-CAPS (p<0.01) by LSI tertiles and shows that abnormal CB-CAPs is more prevalent than low complement at all LSI levels (p<0.01).
Conclusion: These data indicate that abnormalities in the complement system are associated with increased LSI.
Disclosure: C. Arriens, Exagen, 9; S. Narain, Exagen, 2; A. Saxena, Exagen, 2; C. E. Collins, Exagen, 2,Exagen, 8; D. J. Wallace, Exagen, 2,Exagen, 5; E. Massarotti, Exagen, 2; J. Conklin, Exagen, 3; R. Alexander, Exagen, 3; K. C. Kalunian, Exagen, 2; C. Putterman, Exagen, 2; R. Ramsey-Goldman, Exagen, 2; J. P. Buyon, Exagen, 2; A. Askanase, Exagen, 2; R. Furie, Exagen, 2; S. Manzi, Exagen, 2,Exagen, 7,Exagen, 5; J. Ahearn, Exagen, 2,Exagen, 5,Exagen, 7; A. Weinstein, Exagen, 2,Exagen, 5,Exagen, 9; T. Dervieux, Exagen, 3.
To cite this abstract in AMA style:
Arriens C, Narain S, Saxena A, Collins CE, Wallace DJ, Massarotti E, Conklin J, Alexander R, Kalunian KC, Putterman C, Ramsey-Goldman R, Buyon JP, Askanase A, Furie R, Manzi S, Ahearn J, Weinstein A, Dervieux T. Abnormalities in Complement System Are Related to Disease Severity in Systemic Lupus Erythematosus (SLE) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/abnormalities-in-complement-system-are-related-to-disease-severity-in-systemic-lupus-erythematosus-sle/. Accessed .« Back to ACR/ARHP Annual Meeting 2017
ACR Meeting Abstracts - https://acrabstracts.org/abstract/abnormalities-in-complement-system-are-related-to-disease-severity-in-systemic-lupus-erythematosus-sle/