Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: A major unmet need in SLE is the identification of a biomarker that consistently tracks with disease activity. One current approach is measuring complement activation by evaluating consumption of serum C3 and C4. However, since they are acute phase reactants, interpretation of these levels is challenging as serum levels may not decrease until late in a disease flare. iC3b is a proteolytically derived molecule of C3b, and increases with complement activation. iC3b/C3 ratio measures complement consumption relative to production, which may provide for a more accurate assessment of complement activation. We hypothesize that blood iC3b and iC3b/C3 levels will provide a more specific and reliable marker of complement activation and disease activity in SLE.
Methods: 137 adult SLE patients were enrolled in this prospective, longitudinal, observational study. 79 patients with 3-7 study visits were used for this longitudinal analysis. C3 and C4 were measured by nephelometry; iC3b by a lateral flow assay using an investigational medical device. SLE disease activity was measured using the SLEDAI 2K Responder Index-50 instrument. Multilevel regression models were performed to examine associations for SLE disease activity. Ordinal logistic regression models with generalized estimating equation modeling (GEE) were used to examine associations for clinically meaningful changes since the outcome variable is ordinal (i.e. clinical deterioration, stability, and improvement). Odds ratios and 95% confidence intervals for iC3b, C3, iC3b/C3 ratios, C4, ESR, CRP, dsDNA values, prednisone usage, and race were estimated using Proc GLIMMIX and Proc GENMOD (SAS v9.4).
Results: Blood levels of iC3b, C3, iC3b/C3 ratio, C4, dsDNA, and prednisone use each correlated with SLE disease activity. Multilevel multiple logistic regression analysis revealed only iC3b/C3 ratio, dsDNA levels, and prednisone use were significant predictors of disease activity (Table 1A). To determine whether iC3b/C3 ratio can predict clinically meaningful changes in SLE disease activity, we evaluated the interpatient longitudinal associations between clinical deterioration, stability, and improvement and iC3b/C3 ratios. Only iC3b/C3 ratio and prednisone use significantly predicted clinically meaningful changes in disease activity (Table 1B).
Conclusion: In this prospective, longitudinal study, blood iC3b/C3 ratios are predictive of active SLE disease. Furthermore, iC3b/C3 ratio is predictive of clinical meaningful changes in SLE disease activity. These data warrant further investigation of iC3b/C3 ratio as a potential biomarker for SLE disease activity.
To cite this abstract in AMA style:Kim A, Sen D, Strand V, Fu QJ, Mathis N, Bruchas R, Staten N, Schmidt M, Olson P, Stiening C, Atkinson J. Complement Split Product iC3b and C3 Blood Levels Best Associate with Active and Clinically Meaningful Changes in SLE Disease Activity [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/complement-split-product-ic3b-and-c3-blood-levels-best-associate-with-active-and-clinically-meaningful-changes-in-sle-disease-activity/. Accessed October 31, 2020.
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