Session Information
Date: Sunday, November 8, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session I
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 (Gabay
& Kushner, NEJM, 340:448, 1999), interpretation of these
levels is challenging as serum levels may not decrease until late in a disease
flare (Sturfelt & Sjoholm,
Int Arch Allergy Appl
Immunol, 75:75,
1984). 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 as a more specific and reliable
marker of complement activation and disease activity in SLE.
Methods: 90 adult SLE patients were enrolled in this observational study,
encompassing 188 longitudinal visits. C3 and C4 were measured by nephelometry; iC3b using the Kypha
lateral flow assay test. Linear models analysis was used to generate predictive
models of S2K RI-50 scores using iC3b, C3, iC3b/C3 ratio, C4, anti-dsDNA Abs, ESR, and CRP from single visit data. Mixed model
repeated measures analysis was used to evaluate longitudinal data.
Results: Using single visit data, blood levels of iC3b, C3, iC3b/C3 ratio,
C4, and ESR each correlated with SLE disease activity (Table 1). Linear models
analysis yielded a predictive model using iC3b/C3 ratio, C4, and ESR. In the
longitudinal dataset, after modeling for variance structure, S2K RI-50 scores
increased by 0.52 for every 1 unit increase in iC3b/C3 ratios (Table 2). C4 was
also found to mildly influence S2K RI-50 scores.
Conclusion: iC3b/C3 ratios correlated with S2K RI-50 scores and linear model
analysis confirmed the predictive value of iC3b to S2K RI-50 scores. After
adjusting for both correlation and other covariates, the longitudinal data
further established a significant relationship between iC3b/C3 ratios and SLE
disease activity. These data warrant further investigation of iC3b as a
potential biomarker for disease activity in SLE.
To cite this abstract in AMA style:
Kim A, Strand V, Mathis N, Sen D, Miner J, Schramm E, Bruchas R, Staten N, Olson P, Stiening C, Atkinson J. Circulating Levels of iC3b and C3 Correlate with Sledai-2K Responder Index-50 (S2K RI-50) Disease Activity Scores: The Castle (Complement Activation Signatures in Systemic Lupus Erythematosus) Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/circulating-levels-of-ic3b-and-c3-correlate-with-sledai-2k-responder-index-50-s2k-ri-50-disease-activity-scores-the-castle-complement-activation-signatures-in-systemic-lupus-erythematosus-study/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-levels-of-ic3b-and-c3-correlate-with-sledai-2k-responder-index-50-s2k-ri-50-disease-activity-scores-the-castle-complement-activation-signatures-in-systemic-lupus-erythematosus-study/