Evidence map›Paper›PMID 37189377›Full record

ArticleBiomolecules2023

Anti-Citrullinated Protein Antibody Reactivity towards Neutrophil-Derived Antigens: Clonal Diversity and Inter-Individual Variation.

Alexandra Cîrciumaru, Marcelo Gomes Afonso, Heidi Wähämaa, Akilan Krishnamurthy, Monika Hansson, Linda Mathsson-Alm, Márton Keszei, Ragnhild Stålesen, Lars Ottosson, Charlotte de Vries and 7 more

Open access · goldAbstract read
In one paragraph

Article in Biomolecules, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.3field-weighted citation impact, top 19% of its field
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

2 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Review
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

17 authors at 4 institutions in 2 countries.

Alexandra CîrciumaruDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
Marcelo Gomes AfonsoDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.ORCID 0000-0002-6661-4158
Heidi WähämaaDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
Akilan KrishnamurthyDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
Monika HanssonDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.ORCID 0009-0002-5481-1557
Linda Mathsson-AlmThermo Fisher Scientific, 75450 Uppsala, Sweden.
Márton KeszeiDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 17165 Stockholm, Sweden.
Ragnhild StålesenDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
Lars OttossonDivision of Pediatric Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, 17176 Stockholm, Sweden.
Charlotte de VriesDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.ORCID 0000-0003-4513-4128
Miriam A ShelefDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.ORCID 0000-0002-8842-0303
Vivianne MalmströmDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.ORCID 0000-0001-9251-8082
Lars KlareskogDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
Anca I CatrinaDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
Caroline GrönwallDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.
Aase HensvoldDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.ORCID 0000-0002-7669-3777
Bence RéthiDivision of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, 17176 Stockholm, Sweden.ORCID 0000-0001-8220-5015
Karolinska University Hospital · SEKarolinska Institutet · SEUniversity of Wisconsin–Madison · USUppsala University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWhy the adaptive immune system turns against citrullinated antigens in rheumatoid arthritis (RA) and whether anti-citrullinated protein antibodies (ACPAs) contribute to pathogenesis are questions that have triggered intense research, but still are not fully answered. Neutrophils may be crucial in this context, both as sources of citrullinated antigens and also as targets of ACPAs. To better understand how ACPAs and neutrophils contribute to RA, we studied the reactivity of a broad spectrum of RA patient-derived ACPA clones to activated or resting neutrophils, and we also compared neutrophil binding using polyclonal ACPAs from different patients.

methodsNeutrophils were activated by Ca

resultsACPAs broadly targeted NET-like structures, but did not bind to intact cells or influence NETosis. We observed high clonal diversity in ACPA binding to neutrophil-derived antigens. PAD2 was dispensable, but most ACPA clones required PAD4 for neutrophil binding. Using ACPA preparations from different patients, we observed high patient-to-patient variability in targeting neutrophil-derived antigens and similarly in another cellular effect of ACPAs, the stimulation of osteoclast differentiation.

conclusionsNeutrophils can be important sources of citrullinated antigens under conditions that lead to PAD4 activation, NETosis and the extrusion of intracellular material. A substantial clonal diversity in targeting neutrophils and a high variability among individuals in neutrophil binding and osteoclast stimulation suggest that ACPAs may influence RA-related symptoms with high patient-to-patient variability.

Indexed as

Anti-Citrullinated Protein AntibodiesArthritis, RheumatoidAminosalicylic AcidsAnimalsClone CellsMiceNeutrophilsacetyl 4-aminosalicylic acidAminosalicylic AcidsAnti-Citrullinated Protein AntibodiesACPAcitrullinationNETosisneutrophilrheumatoid arthritis

Identifiers

PMID37189377
PMCPMC10135477
OpenAlexW4362468646

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.