Sensitivity and specificity of plasma and urine complement split products as indicators of lupus disease activity

Abstract

Objective. To determine if measurement of serum complement split products (C4d, Bb, C5b-9) is better than conventional C3 and C4 measurements in distinguishing patients with varying degrees of lupus disease activity, and to determine if the presence of C3d in urine is helpful in distinguishing lupus patients with from those without early lupus nephritis.Methods. Lupus disease activity was prospectively determined at 3 consecutive visits an average of 4 months apart, using the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and physician global assessment (PGA). Blood samples were evaluated for the presence of C4d, Bb, and C5b-9 by quantitative microsassay plate enzyme immunoassay at each patient visit. We characterized urinary excretion of C3 fragments (with attention to C3d) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Western blotting.Results. Thirty-one SLE patients were enrolled in the study. The mean SLAM score and the mean SLEDAI score each correlated well with the PGA at all 3 visits. A SLAM score of 6 and a SLEDAI score of 4 had the best overall sensitivity and specificity for predicting moderate-to-severe disease activity by PGA (100% and 73%, respectively, for the SLAM and 86% and 94%, respectively, for the SLEDAI). Serum C4d and Bb were more sensitive indicators of current moderate-to-severe lupus disease activity at all 3 visits than were serum C5b-9, C3, and C4. C3 and C4 were more specific indicators of moderate-to-severe disease activity. Serum C4d and Bb were more sensitive at predicting moderateto-severe disease activity at subsequent visits than were C5b-9, C3, and C4. Urine C3d was better than C3, plasma C4d, Bb, C5b-9 and anti-double-stranded DNA antibody in distinguishing patients with from those without acute lupus nephritis (P = 0.02).

Antibodies reactive to cleaved sites in complement proteins enable highly specific measurement of soluble markers of complement activation

“…The most widely used assay for assessment of soluble C4d is manufactured by Quidel and has been used in a number of clinical studies regarding vasculitis (Gou et al, 2013), cardiac arrest (Bisschops et al, 2012) (Jenei et al, 2014), graft rejection (Flechner et al, 2010), mixed cryoglobulinemia (Sansonno et al, 2009), Sjögren's syndrome (Sudzius et al, 2014), lupus (Manzi et al, 1996) and lung cancer (Ajona et al, 2013). According to the manufacturer, this ELISA is based on a neoepitope C4d catching antibody and detection is completed by goat polyclonal anti-C4d.…”

Markers of childhood lupus nephritis indicating disease activity

“…Though, various studies have shown relationships between complement consumption and SLE disease activity, most have been done in adults [22][23][24]. Studies in children with LN are limited and restricted to the analysis of individual parameters [25,26].…”

Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus

“…Although serum levels of C3, C4, and their activation-derived products are frequently used to monitor disease activity in SLE, their value as biomark-ers is a subject of controversy (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). These observations have led us to consider measurement of complement activation products bound to circulating blood cells (14,15).…”