Evidence map›Paper›PMID 32423478›Full record

ArticleBMC immunology2020

Multi-HLA class II tetramer analyses of citrulline-reactive T cells and early treatment response in rheumatoid arthritis.

Christina Gerstner, Sara Turcinov, Aase H Hensvold, Karine Chemin, Hannes Uchtenhagen, Tamara H Ramwadhdoebe, Anatoly Dubnovitsky, Genadiy Kozhukh, Lars Rönnblom, William W Kwok and 4 more

Open access · goldAbstract read
In one paragraph

Article in BMC immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

19 citing papers in PubMed, 48 citations in OpenAlex.

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  15. MiR-330-5p inhibits intervertebral disk degeneration via targeting CILP.Journal of orthopaedic surgery and research · 2021
    Article
  16. Review
  17. Journal of translational autoimmunity · 2021
    Article
  18. The Role ofFrontiers in cellular and infection microbiology · 2021
    Review
  19. 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

14 authors at 4 institutions in 3 countries.

Christina GerstnerDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Sara TurcinovDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Aase H HensvoldDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Karine CheminDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Hannes UchtenhagenDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Tamara H RamwadhdoebeDepartment of Clinical Immunology and Rheumatology and Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands.
Anatoly DubnovitskyDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Genadiy KozhukhDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Lars RönnblomDepartment of Medical Sciences, Rheumatology, Science for Life Laboratory, Uppsala, Sweden.
William W KwokTranslational Research Program, BRI at Virginia Mason, Seattle, (WA), USA.
Adnane AchourScience for Life Laboratory, Department of Medicine Solna, Karolinska Institutet & Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
Anca I CatrinaDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
Lisa G M van BaarsenDepartment of Clinical Immunology and Rheumatology and Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands.
Vivianne MalmströmDivision of Rheumatology, Department of Medicine Solna, Center for Molecular Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden. vivianne.malmstrom@ki.se.ORCID 0000-0001-9251-8082
Karolinska University Hospital · SEAmsterdam UMC Location University of Amsterdam · NLVirginia Mason Medical Center · USScience for Life Laboratory · SE

Funding

FP7 Health FP7-HEALTH-F2-2012-305549Innovative Medicines Initiative BTCure 115142Innovative Medicines Initiative RTCure 777357Margareta af Ugglas Foundation not applicableReumaNederland 11-1-308ReumaNederland 14-2-403Reumatikerförbundet R-481771Stiftelsen Konung Gustaf V:s 80-årsfond FAI-2016-0312Vetenskapsrådet 2015-02900
6 · The paper itself

Abstract

backgroundHLA class II tetramers can be used for ex vivo enumeration and phenotypic characterisation of antigen-specific CD4+ T cells. They are increasingly applied in settings like allergy, vaccination and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic autoimmune disorder for which many autoantigens have been described.

resultsUsing multi-parameter flow cytometry, we developed a multi-HLA class II tetramer approach to simultaneously study several antigen specificities in RA patient samples. We focused on previously described citrullinated HLA-DRB1*04:01-restricted T cell epitopes from α-enolase, fibrinogen-β, vimentin as well as cartilage intermediate layer protein (CILP). First, we examined inter-assay variability and the sensitivity of the assay in peripheral blood from healthy donors (n = 7). Next, we confirmed the robustness and sensitivity in a cohort of RA patients with repeat blood draws (n = 14). We then applied our method in two different settings. We assessed lymphoid tissue from seropositive arthralgia (n = 5) and early RA patients (n = 5) and could demonstrate autoreactive T cells in individuals at risk of developing RA. Lastly, we studied peripheral blood from early RA patients (n = 10) and found that the group of patients achieving minimum disease activity (DAS28 < 2.6) at 6 months follow-up displayed a decrease in the frequency of citrulline-specific T cells.

conclusionsOur study demonstrates the development of a sensitive tetramer panel allowing simultaneous characterisation of antigen-specific T cells in ex vivo patient samples including RA 'at risk' subjects. This multi-tetramer approach can be useful for longitudinal immune-monitoring in any disease with known HLA-restriction element and several candidate antigens.

Indexed as

AdultAgedArthritis, RheumatoidCD4-Positive T-LymphocytesCitrullineEpitopes, T-LymphocyteExtracellular Matrix ProteinsFemaleFibrinogenFlow CytometryHistocompatibility Antigens Class IIHumansMaleMiddle AgedPyrophosphatasesVimentinCitrullineEpitopes, T-LymphocyteExtracellular Matrix ProteinsFibrinogenHistocompatibility Antigens Class IIPyrophosphatasesVimentinAutoimmune diseaseAutoreactive CD4+ T lymphocytesCitrullinationMulti-MHC class II tetramer assay

Identifiers

PMID32423478
PMCPMC7236297
OpenAlexW3027233559

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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.