Evidence map›Paper›PMID 40624574›Full record

ArticleArthritis research & therapy2025

Insights into the detection of AMPA cross-reactivity: comparing cyclic peptide- to protein-based assays.

Roxane Biersteker, Aegli Athanasiadou, Stef van der Meulen, Tineke J van Wesemael, Linda M Slot, Theresa Kissel, René E M Toes, Leendert A Trouw, Diane van der Woude

Abstract readComparative Study
PubMed Full text at PMC Publisher
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Article in Arthritis research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Roxane Biersteker *Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
Aegli Athanasiadou *Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
Stef van der MeulenDepartment of Immunology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
Tineke J van WesemaelDepartment of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
Linda M SlotDepartment of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
Theresa KisselDepartment of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
René E M ToesDepartment of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
Leendert A TrouwDepartment of Immunology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands.
Diane van der WoudeDepartment of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, 2333 ZA, The Netherlands. dvanderwoude@lumc.nl.

Funding

European Research Council AdG2019-884796Innovative Medicines Initiative 777357Nederlandse Organisatie voor Wetenschappelijk Onderzoek 09150172110053ReumaNederland LLP5Target to B! LSHM18055-5GF
6 · The paper itself

Abstract

backgroundAutoantibodies targeting antigens carrying distinct post-translational modifications (PTMs), including citrullinated, carbamylated, and acetylated residues, are characteristic for rheumatoid arthritis (RA). These anti-modified protein antibodies (AMPAs) are typically detected using enzyme-linked immunosorbent assays (ELISAs), with peptides or protein antigens carrying these modifications. AMPAs exhibit significant cross-reactivity towards multiple PTMs, and increased cross-reactivity before disease onset may serve as a biomarker of disease progression. However, the impact of antigen backbone variations on cross-reactivity detection remains unclear. Therefore, we investigated how PTM-backbone variations affect AMPA-reactivity detection.

methodsSera of 608 RA patients from the Early Arthritis Clinic (EAC) were measured for AMPA reactivity using modified fetal calf serum (FCS)- and cyclic peptide (CXP2)-based ELISAs. To investigate cross-reactivity patterns, we isolated AMPAs from serum using either modified FCS or peptides and assessed the reactivity of the isolated antibodies towards three different PTMs.

resultsCXP2-based assays reveal a higher proportion of patients with serum reactivity against multiple PTM residues, while FCS-based assays exhibit a more restricted serological profile. When comparing responses to citrullinated versus carbamylated backbones, 61.2% of samples reacted to both PTM-residues on CXP2, while on FCS this percentage significantly decreased to 54.0%. The antigen backbone also influences AMPA isolation, as modified FCS captures AMPAs with a more restricted, less cross-reactive epitope recognition profile compared to those captured with modified peptides.

conclusionAntigen backbones influence the detection of AMPA cross-reactivity. Gaining a better understanding of how PTM backbones affect this detection could provide insights into the structural basis of AMPA reactivity, and refine data interpretation by highlighting how assay choice influences results.

Indexed as

Arthritis, RheumatoidAutoantibodiesPeptides, CyclicAdultAgedCross ReactionsEnzyme-Linked Immunosorbent AssayFemaleHumansMaleMiddle AgedProtein Processing, Post-TranslationalAutoantibodiesPeptides, CyclicACPAAntigen backboneAnti-modified protein antibodiesAutoantibodiesCross-reactivityPost-translational modificationsRheumatoid arthritis

Identifiers

PMID40624574
PMCPMC12232869

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