Evidence map›Paper›PMID 40924449›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Synovial MS4A4A correlates with inflammation and counteracts response to corticosteroids in arthritis.

Marie-Astrid Boutet, Irene Mattiola, Rita Silva-Gomes, Alessandra Nerviani, Marina Sironi, Giulia Maria Ghirardi, Alessia Troilo, Stefano Gianoli, Felice Rivellese, Cankut Cubuk and 11 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

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

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Synovial MS4A4A correlates with inflammation and counteracts response to corticosteroids in arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Stimuli-Responsive Nanoplatforms for Precision Intervention in Rheumatoid Arthritis.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
    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

21 authors.

Marie-Astrid Boutet *Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
Irene Mattiola *Institute of Microbiology, Infectious Diseases and Immunology (I-MIDI), Charité-Universitätsmedizin Berlin Campus Benjamin Franklin, Berlin 12203, Germany.ORCID 0000-0002-2922-9947
Rita Silva-Gomes *Cellular and Humoral Innate Immunity Lab, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano 20089, Milan, Italy.
Alessandra NervianiCentre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
Marina SironiCellular and Humoral Innate Immunity Lab, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano 20089, Milan, Italy.
Giulia Maria GhirardiCentre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
Alessia TroiloCellular and Humoral Innate Immunity Lab, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano 20089, Milan, Italy.
Stefano GianoliCellular and Humoral Innate Immunity Lab, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano 20089, Milan, Italy.
Felice RivelleseCentre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
Cankut CubukCentre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
Katriona GoldmannCentre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
Anna Rita PutignanoCellular and Humoral Innate Immunity Lab, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano 20089, Milan, Italy.
Dario Di SilvestreClinical Proteomics Laboratory, Institute for Biomedical Technologies, Segrate 20054, Milan, Italy.
Andrea LomagnoClinical Proteomics Laboratory, Institute for Biomedical Technologies, Segrate 20054, Milan, Italy.
Elena Monica BorroniCellular and Humoral Innate Immunity Lab, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano 20089, Milan, Italy.
Cristina SobacchiCellular and Humoral Innate Immunity Lab, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano 20089, Milan, Italy.ORCID 0000-0002-2684-7184
Myles J LewisCentre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.
Barbara BottazziCellular and Humoral Innate Immunity Lab, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano 20089, Milan, Italy.ORCID 0000-0002-1930-9257
Massimo Locati *Cellular and Humoral Innate Immunity Lab, Istituto di Ricovero e Cura a Carattere Scientifico Humanitas Research Hospital, Rozzano 20089, Milan, Italy.
Alberto Mantovani *Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.ORCID 0000-0001-5578-236X
Costantino Pitzalis *Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute and Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.

Funding

Fondation pour la recherche medicale ARF202004011Fondazione AIRC per la ricerca sul cancro ETS (AIRC) 21147 and IG grant. n. 30672Fondazione Beppe e Nuccy Angiolini n.a.Fundacao para a ciencia e a tecnologia PhD grant PD/BD114138/2016Institut National de la Santé et de la Recherche Médicale (Inserm) ATIP ProgramMedical Research Council, UK 36661Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR) PRIN2017Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR) SCALE-UPNIHR transitional research fellowiship TRF2018PRIN 2022, "Finanziato dall"Unione europea - Next Generation EU Missione 4 Componente 1 G53D23000720001Versus Arthritis Clinical Lectureship in Exp. medicine and Rheumatology 21890Versus Arthritis Experimental Treatment Centre 20022
6 · The paper itself

Abstract

MS4A4A belongs to the MS4A tetraspan protein superfamily and is selectively expressed by the monocyte-macrophage lineage. In this study, we aimed to evaluate the role of MS4A4A+ macrophages in rheumatoid arthritis (RA) pathogenesis and response to treatment. RNA sequencing and immunohistochemistry of synovial samples from either early treatment-naïve or active chronic RA patients showed that MS4A4A expression positively correlated with synovial inflammation. Synovial macrophages from patients treated with corticosteroids (CS) exhibited an enhanced expression of MS4A4A and Fc γ receptor (FcγR) 3. Accordingly, CS enhanced in vitro the expression of MS4A4A and FcγR3 in human and murine macrophages. In an experimental model of arthritis, Ms4a4a deletion had no effect on the disease course but was associated with enhanced therapeutic response selectively to CS. These results suggest that macrophage expression of MS4A4A represents a biomarker of joint inflammation in RA and that its upregulation in concert with FcγR3 by CS counteracts the therapeutic activity of these drugs. Macrophage MS4A4A may represent a biomarker of joint inflammation in RA and a target to amplify the therapeutic activity of CS.

Indexed as

Adrenal Cortex HormonesArthritis, RheumatoidInflammationSynovial MembraneAnimalsBiomarkersFemaleHumansMacrophagesMaleMiceMiddle AgedReceptors, IgGAdrenal Cortex HormonesBiomarkersReceptors, IgGcorticosteroidsmacrophagesMS4A4Arheumatoid arthritissynovium

Identifiers

PMID40924449
PMCPMC12452939

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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.