Relationship of Circulating Anti-C3b and Anti-C1q IgG to Lupus Nephritis and Its Flare

Abstract

Background and objectives Autoantibodies to complement C1q (anti-C1q) are associated with the diagnosis of lupus nephritis. In this study, we compare anti-C1q IgG with another complement autoantibody, anti-C3b IgG, as a biomarker of lupus nephritis and lupus nephritis flare.Design, setting, participants, & measurements Our investigation involved the Ohio SLE Study, a prospective observational cohort of patients with recurrently active lupus who were followed bimonthly. Serum anti-C1q and anti-C3b IgG levels were assessed cross-sectionally by ELISA in 40 normal controls and 114 patients in the Ohio SLE Study (41 nonrenal and 73 lupus nephritis) at study entry, and longitudinally in a subset of patients in the Ohio SLE Study with anti-C1q-positive lupus nephritis in samples collected every 2 months for 8 months leading up to lupus nephritis flare (n=16 patients). ResultsIn the cross-sectional analysis, compared with anti-C1q IgG, anti-C3b IgG was less sensitive (36% versus 63%) but more specific (98% versus 71%) for lupus nephritis. Only anti-C3b IgG was associated with patients with lupus nephritis who experienced at least one lupus nephritis flare during the Ohio SLE Study period (P,0.01). In the longitudinal analysis, circulating levels of anti-C1q IgG increased at the time of lupus nephritis flare only in patients who were anti-C3b positive (P=0.02), with significant increases occurring from 6 (38% increase) and 4 months (41% increase) before flare. Anti-C3b IgG levels also trended up at lupus nephritis flare, although the change did not reach statistical significance (P=0.07). Neither autoantibody increased 2 months before flare.Conclusions Although not as prevalent as anti-C1q IgG, anti-C3b IgG showed nearly complete specificity for lupus nephritis. The presence of anti-C3b IgG identified patients with lupus nephritis who were prone to flare and in whom serial measurements of markers associated with complement, such as anti-C1q IgG, may be useful to monitor lupus nephritis activity.

Update on Lupus Nephritis

“…In this regard, autoantibodies to C components that are found in patients with lupus may be important in the development of LN. In a cohort of 114 lupus patients, 23% of patients had autoantibodies to C component C1q and to C3b (43). In these dual-antibody-positive patients who were prospectively followed, anti-C3b and anti-C1q levels tended to increase in the months leading up to renal flare.…”

Lupus Nephritis in the Era of Biomarkers

“…Birmingham et al (9) note that, as expected, C3 levels were inversely correlated with anti-C3b antibodies, and they suggest that C3b neoepitopes forming at sites of kidney damage may be driving the formation of anti-C3b antibodies. This study carries several major limitations.…”

The role of the alternative pathway of complement activation in glomerular diseases

“…In another study, antibodies against C3b, although less frequent than that against C1q, showed a higher specificity for LN, particularly for the prediction of renal flare [127]. Thus, Bb and anti-C3b antibodies appear as new markers for monitoring LN activity [125,127].…”

“…To date, the autoantibodies against C3 and C3b have been reported in LN (Table 2) [126,127]. In the Bulgarian population, anti-C3 antibodies were present in 31% of patients (in 12 of total 39 individuals), and they correlated positively with anti-dsDNA antibodies levels, as well as with the severity of LN.…”