Evidence map›Paper›PMID 40148491›Full record

ArticleScientific reports2025

Factor H-related 2 levels dictate FHR dimer composition.

Bert R J Veuskens, Mieke C Brouwer, Gerard van Mierlo, Judy Geissler, Karin van Leeuwen, Maaike Derlagen, Nadia C H Keijzer, Mark Hoogenboezem, Taco W Kuijpers, Richard B Pouw

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In one paragraph

Article in Scientific reports, 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

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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

10 authors.

Bert R J VeuskensSanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands.
Mieke C BrouwerSanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands.
Gerard van MierloSanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands.
Judy GeisslerSanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands.
Karin van LeeuwenSanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands.
Maaike DerlagenSanquin Diagnostic Services, 1066 CX, Amsterdam, The Netherlands.
Nadia C H KeijzerSanquin Diagnostic Services, 1066 CX, Amsterdam, The Netherlands.
Mark HoogenboezemSanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands.
Taco W KuijpersSanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands.
Richard B PouwSanquin Research and Landsteiner Laboratory of the Amsterdam University Medical Centers, University of Amsterdam, Plesmanlaan 125, 1066 CX, Amsterdam, The Netherlands. richard.pouw@sanquin.nl.

Funding

European Union's Horizon 2020 research and innovation programme 899163Sanquin Research Fund SRF-YIA-23-06
6 · The paper itself

Abstract

Factor H-related (FHR) protein 1 and 2 form dimers resulting in FHR-1 and -2 homodimers, and FHR-1/2 heterodimers. Dimerization is hypothesized to further increase their antagonistic function with complement regulator factor H (FH). So far, only FHR-1 homodimers and FHR-1/2 heterodimers could be quantified in a direct way. With the reported genetic associations between CFHR2 and complement-related diseases such as age related macular degeneration and C3-glomerulopathy, direct assessment of FHR-2/2 levels determining the dimer distribution of FHR-1 and -2 is needed to further elucidate their role within complement regulation. Therefore, novel in-house generated FHR-2 antibodies were used to develop a specific ELISA to enable direct quantification of FHR-2 homodimers. Allowing for the first time the accurate measurement of all FHR-1 and -2 containing dimers in a large cohort of healthy donors. By using native FHR-1 and -2 or deficient plasma, we determined the stability, kinetics and distribution of FHR-1 and -2 dimers. Additionally, we show how genetic variants influence dimer levels. Our results confirm a rapid, dynamic, dimer formation in plasma and show FHR-1/2 dimerization rearches a distribution equilibrium that is limited by the relative low levels of FHR-2 in relation to its dimerization partner FHR-1.

Indexed as

Complement C3b Inactivator ProteinsEye ProteinsProtein MultimerizationEnzyme-Linked Immunosorbent AssayHumansCFHR1 protein, humanComplement C3b Inactivator ProteinsEye ProteinsComplement systemDimerizationFHR-1FHR-2

Identifiers

PMID40148491
PMCPMC11950314

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