Evidence map›Paper›PMID 40280868›Full record

ArticleRheumatology (Oxford, England)2025

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

Agneta Zickert, Caroline Grönwall, Anna Juto, Lina-Marcela Diaz-Gallo, Sepehr Sarrafzadeh Zargar, Ann Mongan, Henk-Andre Kroon, Myriam Martin, Anna M Blom, Edmund Chang and 1 more

Abstract read
In one paragraph

Article in Rheumatology (Oxford, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Agneta ZickertDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Stockholm, Sweden.
Caroline GrönwallDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Stockholm, Sweden.ORCID 0000-0002-9111-5537
Anna JutoDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Stockholm, Sweden.
Lina-Marcela Diaz-GalloDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Stockholm, Sweden.ORCID 0000-0002-5688-0102
Sepehr Sarrafzadeh ZargarDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Stockholm, Sweden.
Ann MonganAnnexon Biosciences, Brisbane, CA, USA.
Henk-Andre KroonAnnexon Biosciences, Brisbane, CA, USA.
Myriam MartinDepartment of Translational Medicine, Lund University, Malmö, Sweden.
Anna M BlomDepartment of Translational Medicine, Lund University, Malmö, Sweden.ORCID 0000-0002-1348-1734
Edmund ChangAnnexon Biosciences, Brisbane, CA, USA.
Iva GunnarssonDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Stockholm, Sweden.

Funding

Annexon Biosciences, King Gustaf V's Memorial FundRegion Stockholm and Region SkåneSwedish Rheumatism Association, Stig och Gunborg Westman's Research FundThe Swedish Kidney Foundation
6 · The paper itself

Abstract

objectiveThe investigation of complement factors in lupus nephritis (LN) in relation to treatment response and the impact of underlying genetics of C4.

methodsSeventy-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.

resultsAt 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.

conclusionAll 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.

Indexed as

Complement C4Complement C4bImmunosuppressive AgentsLupus NephritisPeptide FragmentsAdultBiomarkersBiopsyComplement C3DNA Copy Number VariationsFemaleHumansKidneyMaleMiddle AgedTreatment OutcomeBiomarkersComplement C3Complement C4Complement C4bcomplement C4dImmunosuppressive AgentsPeptide FragmentsC4dcomplementlupus nephritissystemic lupus erythematosus

Identifiers

PMID40280868
PMCPMC12316364

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.