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Measuring plasma C4D to monitor immune complexes in lupus nephritis

Kraaij, Tineke ; Nilsson, Sara C. LU ; Van Kooten, Cees ; Okrój, Marcin LU ; Blom, Anna M. LU and Teng, Yk Onno (2019) In Lupus Science and Medicine 6(1).
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C4d, complement, immunoglobulin-mediated membranoproliferative glomerulonephritis, lupus nephritis, systemic lupus erythematosus
in
Lupus Science and Medicine
volume
6
issue
1
article number
e000326
publisher
BMJ Publishing Group
external identifiers
  • scopus:85066946560
ISSN
2053-8790
DOI
10.1136/lupus-2019-000326
language
English
LU publication?
yes
id
55237dcc-9d73-4acc-b7e2-d25a30c4fdb6
date added to LUP
2019-07-05 13:01:45
date last changed
2019-11-25 09:32:50
@article{55237dcc-9d73-4acc-b7e2-d25a30c4fdb6,
  abstract     = {<p>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&lt;0.001) and anti-C1q (R=0.65, p&lt;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&lt;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.</p>},
  author       = {Kraaij, Tineke and Nilsson, Sara C. and Van Kooten, Cees and Okrój, Marcin and Blom, Anna M. and Teng, Yk Onno},
  issn         = {2053-8790},
  language     = {eng},
  number       = {1},
  publisher    = {BMJ Publishing Group},
  series       = {Lupus Science and Medicine},
  title        = {Measuring plasma C4D to monitor immune complexes in lupus nephritis},
  url          = {http://dx.doi.org/10.1136/lupus-2019-000326},
  doi          = {10.1136/lupus-2019-000326},
  volume       = {6},
  year         = {2019},
}