Evidence map›Paper›PMID 35027076›Full record

ArticleArthritis research & therapy2022

Characterization and use of the ECV304 autoantigenic citrullinome to understand anti-citrullinated protein/peptide autoantibodies in rheumatoid arthritis.

Natalia Regine de França, Henri André Ménard, Maximilien Lora, Zhijie Zhou, Joyce Rauch, Carol Hitchon, Luís Eduardo Coelho Andrade, Inés Colmegna

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.3field-weighted citation impact, top 42% 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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

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

8 authors at 3 institutions in 2 countries.

Natalia Regine de FrançaDivision of Rheumatology, Department of Medicine, McGill University, The Research Institute of the McGill University Health Centre, 1001 Décarie Boulevard, Montréal, QC, H4A 3J1, Canada.
Henri André MénardDivision of Rheumatology, Department of Medicine, McGill University, The Research Institute of the McGill University Health Centre, 1001 Décarie Boulevard, Montréal, QC, H4A 3J1, Canada.
Maximilien LoraDivision of Rheumatology, Department of Medicine, McGill University, The Research Institute of the McGill University Health Centre, 1001 Décarie Boulevard, Montréal, QC, H4A 3J1, Canada.
Zhijie ZhouDivision of Rheumatology, Department of Medicine, McGill University, The Research Institute of the McGill University Health Centre, 1001 Décarie Boulevard, Montréal, QC, H4A 3J1, Canada.
Joyce RauchDivision of Rheumatology, Department of Medicine, McGill University, The Research Institute of the McGill University Health Centre, 1001 Décarie Boulevard, Montréal, QC, H4A 3J1, Canada.
Carol HitchonSection of Rheumatology, Department of Medicine, University of Manitoba, Winnipeg, MB, Canada.
Luís Eduardo Coelho AndradeDivision of Rheumatology, Paulista School of Medicine, Federal University of Sao Paulo, Sao Paulo, Brazil.
Inés ColmegnaDivision of Rheumatology, Department of Medicine, McGill University, The Research Institute of the McGill University Health Centre, 1001 Décarie Boulevard, Montréal, QC, H4A 3J1, Canada. ines.colmegna.med@ssss.gouv.qc.ca.
McGill University Health Centre · CAUniversidade Federal de São Paulo · BRUniversity of Manitoba · CA

Funding

CIHR 201209MOP-287233-CIB_CFAC-189937
6 · The paper itself

Abstract

backgroundAnti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA). In vivo, ACPAs target peptidyl-citrulline epitopes (cit-) in a variety of proteins (cit-prot-ACPAs) and derived peptides (cit-pept-ACPAs) generated via the peptidylarginine deiminase (PAD) isoenzymes. We aimed to identify a cell line with self-citrullination capacity, to describe its autoantigenic citrullinome, and to test it as a source of autocitrullinated proteins and peptides.

methodsHuman cell lines were screened for cit-proteins by Western blot. PAD isoenzymes were identified by RT-PCR. Autocitrullination of ECV304 was optimized, and the ECV304 autocitrullinomes immunoprecipitated by sera from three RA patients were characterized by mass spectrometry. Cit-pept-ACPAs were detected using anti-CCP2 ELISA and cit-prot-ACPAs, by an auto-cit-prot-ECV304 ELISA. Sera from 177 RA patients, 59 non-RA rheumatic disease patients and 25 non-disease controls were tested.

resultsOf the seven cell lines studied, only ECV304 simultaneously overexpressed PAD2 and PAD3 and its extracts reproducibly autocitrullinated self and non-self-proteins. Proteomic analysis of the cit-ECV304 products immunoprecipitated by RA sera, identified novel cit-targets: calreticulin, profilin 1, vinculin, new 14-3-3 protein family members, chaperones, and mitochondrial enzymes. The auto-cit-prot-ECV304 ELISA had a sensitivity of 50% and a specificity of 95% for RA diagnosis.

conclusionsECV304 cells overexpress two of the PAD isoenzymes capable of citrullinating self-proteins. These autocitrullinated cells constitute a basic and clinical research tool that enable the detection of cit-prot-ACPAs with high diagnostic specificity and allow the identification of the specific cit-proteins targeted by individual RA sera.

Indexed as

Arthritis, RheumatoidAutoantibodiesAutoantigensCitrullineHumansPeptidesProteomicsAutoantibodiesAutoantigensCitrullinePeptidesACPAsAutocitrullinomeECV304Peptidylarginine deiminasesRheumatoid arthritis

Identifiers

PMID35027076
PMCPMC8756661
OpenAlexW4206043787

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.