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Abstract
Background Complement activation is a hallmark of SLE pathophysiology. We previously found that iC3b/C3 ratios associated with active disease and clinically meaningful changes in SLE disease activity. Since SLE is more severe in nonwhite populations, we hypothesized that iC3b/C3 ratios would be a more sensitive marker of disease activity in nonwhite populations. Thus, we examined the relationship of iC3b/C3 ratios between African-American (AA) and White subjects with classified SLE seen at the Washington University.
Methods 159 adult SLE patients were enrolled in this 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.
Results iC3b/C3 ratios and C3 associated with active disease in AA and White SLE subjects, with the association of the iC3b/C3 ratio in AA was stronger (figure 1). In addition, AA with SLE associated C4, ESR, and dsDNA with active disease, while Whites associated with CRP. In multiple regression analysis, iC3b/C3 ratios independently associated with active disease in both groups, although the effect was more pronounced in AA (AA: OR=1.48, 95% CI=1.21–1.82; Whites: OR=1.17, 95% CI=1.02–1.34). Furthermore, in univariate regression analysis, only the iC3b/C3 ratio in AA associated with clinically meaningful changes in disease activity.
Conclusions iC3/C3 ratios better correlated with active disease in AA compared to Whites. Furthermore, iC3b/C3 ratios correlated with clinically meaningful changes in disease activity only in AA.
Univariate regression analysis of the association of biochemical variables with active SLE. Red (AA) and pink (whites) whiskers represent statistically significant variables, while grey (white) and black (AA) represent non-significant variables
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