Measuring plasma C4D to monitor immune complexes in lupus nephritis

Kraaij, T.; Nilsson, S.C.; Kooten, C. van; Okroj, M.; Blom, A.M.; Teng, Y.K.O. (2019)

Article / Letter to editor

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 antidsDNA (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.

• All authors: Kraaij, T.; Nilsson, S.C.; Kooten, C. van; Okroj, M.; Blom, A.M.; Teng, Y.K.O.
• Date: 2019-01-01
• Journal: Lupus Science & Medicine
• Volume: 6
• Issue: 1
• DOI: doi:10.1136/lupus-2019-000326