Measuring plasma C4D to monitor immune complexes in lupus nephritis. Issue 1 (3rd June 2019)

• Record Type: Journal Article
• Authors: Kraaij, Tineke; Nilsson, Sara C.; van Kooten, Cees; Okrój, Marcin; Blom, Anna M; Teng, YK Onno
• Is Part Of: Lupus science & medicine. Volume 6:Issue 1(2019)
• Publication Date: 2019-06-03
• Subjects: systemic lupus erythematosus -- lupus nephritis -- immunoglobulin-mediated membranoproliferative glomerulonephritis -- complement -- C4d; Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1136/lupus-2019-000326
• Languages: English
• ISSNs: 2398-8851

Abstract

Abstract : Objective: Because currently available assays that measure circulating immune complexes (ICx) are suboptimal, a novel assay was recently developed measuring C4d, a stable product of activation of the classical complement pathway. The present study aimed to establish the value of measuring plasma C4d levels in a longitudinal cohort of patients with severe refractory SLE who were treated with a combination therapy of rituximab with belimumab (RTX+BLM). Methods: Fifteen patients with SLE who were treated with RTX+BLM in a phase 2A, open label study were included to sequentially measure plasma C4d levels and correlated to well-established markers of ICx-formation, that is, autoantibodies against double-stranded (ds) DNA, autoantibodies against C1q and proteinuria. The performance of plasma C4d measurements, C4 measurements and the ratio of C4d over C4 (C4d:C4) was evaluated. Results: After establishing that on RTX+BLM treatment kinetics of C4d levels was distinct from traditional C3 and C4 levels, we found strong correlation of C4d:C4 with anti-dsDNA (R=0.76, p<0.001) and anti-C1q (R=0.65, p<0.001) autoantibody levels, which outperformed both stand-alone C4 and C4d levels. Additionally, changes in C4d:C4 over time correlated strongly with changes in proteinuria (R=0.59, p<0.001) as well as anti-dsDNA (R=0.46, p=0.003) and anti-C1q (R=0.47, p=0.002). Conclusion: In patients with severe SLE, plasma C4d levels in relation to C4 levels is useful for longitudinal monitoring after RTX+BLM treatment to reflect amelioration of classical complement activation by ICx as well as proteinuria.