Measuring plasma C4D to monitor immune complexes in lupus nephritis

Tineke Kraaij , Sara C. Nilsson , Cees van Kooten , Marcin Okrój , Anna Maria Blom , YK Onno Teng


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.
Author Tineke Kraaij
Tineke Kraaij,,
, Sara C. Nilsson
Sara C. Nilsson,,
, Cees van Kooten
Cees van Kooten,,
, Marcin Okrój (IFB / DMedB)
Marcin Okrój,,
- Department of Medical Biotechnology
, Anna Maria Blom
Anna Maria Blom,,
, YK Onno Teng
YK Onno Teng,,
Journal seriesLupus Science and Medicine, ISSN , e-ISSN 2053-8790, (N/A 70 pkt)
Issue year2019
Publication size in sheets0.5
Article numbere000326
ASJC Classification2700 General Medicine; 2403 Immunology
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa - Użycie Niekomercyjne (CC-BY-NC); with publication
Score (nominal)70
Score sourcejournalList
ScoreMinisterial score = 70.0, 04-02-2020, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.346
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