Date: Monday, November 6, 2017
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
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: 159 adult SLE patients were enrolled in this prospective, longitudinal, observational study. 83 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. Statistical analyses were performed using SAS v9.4. Multilevel regression models examined associations for SLE disease activity. Ordinal logistic regression models with generalized estimating equation modeling (GEE) examined associations for clinically meaningful changes since the outcome variable is ordinal. Odds ratios and 95% confidence intervals were estimated using Proc GLIMMIX and Proc GENMOD. Receiver operator curves and areas under the curve were performed using iC3b/C3 ratios, C3, C4, and dsDNA levels.
Results: Blood levels of iC3b, C3, iC3b/C3 ratio, C4, dsDNA, and prednisone use each correlated with SLE disease activity (Figure 1A). Multilevel multiple logistic regression analysis revealed only iC3b/C3 ratio, dsDNA levels, and prednisone use were significant predictors of disease activity (Figure 1B). 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 significantly predicted clinically meaningful changes in disease activity in multivariate regression analysis. iC3b/C3 ratio also discriminated for active versus inactive disease (AUC=0.657, 95% CI=0.604-0.710).
Conclusion: In this prospective, longitudinal study, blood iC3b/C3 ratios are more strongly associated with active SLE disease compared to other traditional biomarkers of disease activity. Likewise, iC3b/C3 ratio is predictive of clinical meaningful changes in SLE disease activity. Finally, iC3b/C3 ratio discriminated for active SLE. These data suggest iC3b/C3 ratio may provide clinical utility as a biomarker for SLE disease activity.
To cite this abstract in AMA style:Kim A, Sen D, Strand V, Fu QJ, Mathis N, Schmidt M, Bruchas R, Staten N, Olson P, Stiening C, Atkinson J. Blood Levels of Complement Split Product iC3b and C3 Outperform Traditional Biochemical Measures of SLE Disease Activity in Associating with Active and Clinically Meaningful Changes [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/blood-levels-of-complement-split-product-ic3b-and-c3-outperform-traditional-biochemical-measures-of-sle-disease-activity-in-associating-with-active-and-clinically-meaningful-changes/. Accessed September 18, 2021.
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