Measuring plasma C4D to monitor immune complexes in lupus nephritis
(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.
(Less)
- author
- Kraaij, Tineke ; Nilsson, Sara C. LU ; Van Kooten, Cees ; Okrój, Marcin LU ; Blom, Anna M. LU and Teng, Yk Onno
- organization
- publishing date
- 2019
- 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
-
- pmid:31245016
- 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
- 2024-08-21 03:21:26
@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<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.</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}}, keywords = {{C4d; complement; immunoglobulin-mediated membranoproliferative glomerulonephritis; lupus nephritis; systemic lupus erythematosus}}, 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}}, }