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Plasma C4d levels correlate with treatment response and renal activity in proliferative lupus nephritis

Zickert, Agneta ; Grönwall, Caroline ; Juto, Anna ; Diaz-Gallo, Lina Marcela ; Zargar, Sepehr Sarrafzadeh ; Mongan, Ann ; Kroon, Henk Andre ; Martin, Myriam LU orcid ; Blom, Anna M. LU orcid and Chang, Edmund , et al. (2025) In Rheumatology 64(8). p.4825-4833
Abstract

Objective The investigation of complement factors in lupus nephritis (LN) in relation to treatment response and the impact of underlying genetics of C4. Methods Seventy-seven patients with active LN confirmed by a kidney biopsy and in whom second biopsies had been performed after immunosuppressive treatment were included. Complement factors C3, C4, C4d and C4d/C4 ratio were evaluated at the biopsy time points. The gene copy number variations of C4 (C4A and C4B) were also investigated. Results At baseline, 60 patients had class III/IV±V, proliferative LN (PLN) and 17 class V, membranous LN (MLN). Levels of C3 and C4 increased and C4d and C4d/C4 decreased after treatment (P < 0.0001), observed in treatment-responding PLN patients but... (More)

Objective The investigation of complement factors in lupus nephritis (LN) in relation to treatment response and the impact of underlying genetics of C4. Methods Seventy-seven patients with active LN confirmed by a kidney biopsy and in whom second biopsies had been performed after immunosuppressive treatment were included. Complement factors C3, C4, C4d and C4d/C4 ratio were evaluated at the biopsy time points. The gene copy number variations of C4 (C4A and C4B) were also investigated. Results At baseline, 60 patients had class III/IV±V, proliferative LN (PLN) and 17 class V, membranous LN (MLN). Levels of C3 and C4 increased and C4d and C4d/C4 decreased after treatment (P < 0.0001), observed in treatment-responding PLN patients but not in MLN. C4d, C4 and C4d/C4 at second biopsies were associated with clinical response in PLN, and low C4d levels were found in PLN with histopathological response (P = 0.008). Renal activity index at second biopsies correlated to C4d and C4d/C4, but not to C3 or C4. C4 gene copy number variations were not associated with clinical or histopathological response. Conclusion All complement markers were affected by immunosuppressive therapy and associated with response to therapy. Levels of C4d and C4d/C4 at follow-up biopsies showed a strong association with both clinical and histopathological response in PLN. The correlation with elevated C4d and C4d/C4 and persisting high activity index on repeated biopsies strengthens the findings on C4d as a promising biomarker for treatment response in PLN. The C4 genetic variations did not influence C4 levels or response to treatment.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C4d, complement, lupus nephritis, systemic lupus erythematosus
in
Rheumatology
volume
64
issue
8
pages
9 pages
publisher
Oxford University Press
external identifiers
  • pmid:40280868
  • scopus:105012361669
ISSN
1462-0324
DOI
10.1093/rheumatology/keaf160
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s).
id
778a0e13-3bec-4f31-acab-4afdee85f7f4
date added to LUP
2025-12-12 15:45:08
date last changed
2025-12-13 03:00:05
@article{778a0e13-3bec-4f31-acab-4afdee85f7f4,
  abstract     = {{<p>Objective The investigation of complement factors in lupus nephritis (LN) in relation to treatment response and the impact of underlying genetics of C4. Methods Seventy-seven patients with active LN confirmed by a kidney biopsy and in whom second biopsies had been performed after immunosuppressive treatment were included. Complement factors C3, C4, C4d and C4d/C4 ratio were evaluated at the biopsy time points. The gene copy number variations of C4 (C4A and C4B) were also investigated. Results At baseline, 60 patients had class III/IV±V, proliferative LN (PLN) and 17 class V, membranous LN (MLN). Levels of C3 and C4 increased and C4d and C4d/C4 decreased after treatment (P &lt; 0.0001), observed in treatment-responding PLN patients but not in MLN. C4d, C4 and C4d/C4 at second biopsies were associated with clinical response in PLN, and low C4d levels were found in PLN with histopathological response (P = 0.008). Renal activity index at second biopsies correlated to C4d and C4d/C4, but not to C3 or C4. C4 gene copy number variations were not associated with clinical or histopathological response. Conclusion All complement markers were affected by immunosuppressive therapy and associated with response to therapy. Levels of C4d and C4d/C4 at follow-up biopsies showed a strong association with both clinical and histopathological response in PLN. The correlation with elevated C4d and C4d/C4 and persisting high activity index on repeated biopsies strengthens the findings on C4d as a promising biomarker for treatment response in PLN. The C4 genetic variations did not influence C4 levels or response to treatment.</p>}},
  author       = {{Zickert, Agneta and Grönwall, Caroline and Juto, Anna and Diaz-Gallo, Lina Marcela and Zargar, Sepehr Sarrafzadeh and Mongan, Ann and Kroon, Henk Andre and Martin, Myriam and Blom, Anna M. and Chang, Edmund and Gunnarsson, Iva}},
  issn         = {{1462-0324}},
  keywords     = {{C4d; complement; lupus nephritis; systemic lupus erythematosus}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{4825--4833}},
  publisher    = {{Oxford University Press}},
  series       = {{Rheumatology}},
  title        = {{Plasma C4d levels correlate with treatment response and renal activity in proliferative lupus nephritis}},
  url          = {{http://dx.doi.org/10.1093/rheumatology/keaf160}},
  doi          = {{10.1093/rheumatology/keaf160}},
  volume       = {{64}},
  year         = {{2025}},
}