Plasma C4d as marker for lupus nephritis in Systemic Lupus Erythematosus

Abstract

Background: In the present study, we sought to evaluate the complement activation product C4d as a marker for lupus nephritis in systemic lupus erythematosus (SLE). Methods: C4d levels were determined by enzyme-linked immunosorbent assay in plasma samples of patients with established SLE using a novel approach based on detection of a short linear cleavage neoepitope. Cross-sectional associations were studied in 98 patients with SLE with samples taken at lower or higher respective disease activity. Temporal associations were investigated in 69 patients with SLE who were followed longitudinally for up to 5 years. Plasma samples from 77 healthy donors were included as controls. Results: C4d levels were negligible in healthy control subjects and significantly increased in patients with SLE in the cross-sectional study (p < 0.0001). C4d levels discriminated between higher and lower disease activity according to ROC curve analysis (p < 0.001), exhibiting a positive predictive value of 68%. At higher disease activity, C4d levels correlated with the modified Systemic Lupus Erythematosus Disease Activity Index (p = 0.011) and predominantly with lupus nephritis (p = 0.003), exhibiting a sensitivity of 79% to identify patients with nephritis. High C4d levels together with the presence of anti-dsDNA autoantibodies preceded and thus predicted future lupus nephritis in the longitudinal study (OR 5.4,3). When we considered only patients with renal involvement (19 of 69) during the longitudinal study, we found that high C4d levels alone could forecast recurrence of future lupus nephritis (OR 3.3, 95% CI 1.2-9.6).Conclusions: C4d appears to be a valuable marker for use in monitoring of patients with SLE, particularly for lupus nephritis. Importantly, C4d levels can predict impending flares of lupus nephritis and may thus be useful for informing treatment.

54 Blood concentrations of complement split product iC3b and serum C3 associate with systemic lupus erythematosus disease activity

“…Recently, serum and plasma levels of C3dg (33) and plasma levels of C4d (34) were shown to be useful in distinguishing between subjects with SLE and healthy controls. Furthermore, plasma C4d levels correlated with disease activity in patients with SLE and were predictive of the future recurrence of nephritis (34). In summary, complement split products appear to offer promise as biomarkers of SLE disease activity.…”

Association of Blood Concentrations of Complement Split Product iC3b and Serum C3 With Systemic Lupus Erythematosus Disease Activity

“…Recently, serum and plasma levels of C3dg and plasma levels of C4d were shown to be useful in distinguishing between subjects with SLE and healthy controls. Furthermore, plasma C4d levels correlated with disease activity in patients with SLE and were predictive of the future recurrence of nephritis . In summary, complement split products appear to offer promise as biomarkers of SLE disease activity.…”

Urinary C3d is elevated in patients with active Lupus nephritis and a fall in its level after 3 months predicts response at 6 months on follow up

“…Apart from the cross sectional study done in the past by our group, there have been several studies to see the utility of complement degradation products as markers of disease activity, more in plasma than urine. 3–6,15–17 Manzi et al. found plasma C4d and Bb to be a better indicator of moderate to severe disease activity as per Physician global assessment.…”

“…demonstrated higher levels of plasma C4d in SLE as compared to healthy controls and the levels could discriminate between low and high disease activity. 6…”