Dataset Information

Methotrexate Restores CD73 Expression on Th1.17 in Rheumatoid Arthritis and Psoriatic Arthritis Patients and May Contribute to Its Anti-Inflammatory Effect through Ado Production.

ABSTRACT: OBJECTIVES:Th1.17 are highly polyfunctional, potentially harmful CD4+ effector T cells (Teff) through IFN-? and IL-17A coproduction. Th1.17 take part in the pathophysiology of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which their hyper activation results in part from defects in negative regulation mechanisms. We recently demonstrated that the ecto-nucleotidase CD73 delineates a Th1.17-enriched Teff population and acts as an endogenous regulatory mechanism. Because Methotrexate (MTX), used as first line treatment of RA and PsA, increases extracellular concentrations of AMP and immunosuppressive adenosine, we investigated the modulation of CD73 by MTX treatment on Teff in RA/PsA patients. METHODS:In a prospective cohort of 26 RA and 15 PsA patients before or under MTX treatment, we evaluated CD73 expression on blood Teff subsets, their cytokine production and AMPase functions. RESULTS:We showed a decreased CD73 expression on Th1.17 and Th1 in untreated patients compared to healthy donors that was partly restored under MTX. This decrease in untreated patients leads to a halved Ado production by Th1.17 cells. CD73+ Teff remained functional under MTX treatment, but their CD73 re-expression may contribute to control their activation. CONCLUSION:Our study unveils uncovered mode of action of MTX on Teff subsets modulation and in the adenosine-dependent termination of inflammation in RA and PsA.

SUBMITTER: Bossennec M

PROVIDER: S-EPMC6912794 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Methotrexate Restores CD73 Expression on Th1.17 in Rheumatoid Arthritis and Psoriatic Arthritis Patients and May Contribute to Its Anti-Inflammatory Effect through Ado Production.

Bossennec Marion M Rodriguez Céline C Hubert Margaux M Di-Roio Anthony A Machon Christelle C Guitton Jérôme J Battiston-Montagne Priscilla P Couturier Mathilde M Marotte Hubert H Caux Christophe C Coury Fabienne F Ménétrier-Caux Christine C

Journal of clinical medicine 20191103 11

<h4>Objectives</h4>Th1.17 are highly polyfunctional, potentially harmful CD4<sup>+</sup> effector T cells (Teff) through IFN-γ and IL-17A coproduction. Th1.17 take part in the pathophysiology of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which their hyper activation results in part from defects in negative regulation mechanisms. We recently demonstrated that the ecto-nucleotidase CD73 delineates a Th1.17-enriched Teff population and acts as an endogenous regulatory mechanism. Be ...[more]

PMID: 31684171

Similar Datasets

Project description:BackgroundDifferential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Abneg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Abneg RA and test their predictive value of therapeutic response.MethodsThirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Abneg RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68+, CD3+, CD20+, CD21+, CD117+, and CD138+ cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Abneg RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations.ResultsAt study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68+ and sublining CD21+, CD20+, and CD3+ cells than Abneg RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117+ cells (p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Abneg RA patients. Conversely, Abneg RA patients showed higher IHC score of CD138+ cells, irrespective to the therapeutic scheme (p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3+ cells compared to PsA patients not reaching this outcome (p = 0.02); conversely, naive Abneg RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of sublining CD68+ cells compared to Abneg RA patients not reaching this outcome (p < 0.001).ConclusionsCD117+ and CD138+ cells are differentially distributed among PsA and Abneg RA. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.

Dataset Information

Methotrexate Restores CD73 Expression on Th1.17 in Rheumatoid Arthritis and Psoriatic Arthritis Patients and May Contribute to Its Anti-Inflammatory Effect through Ado Production.

Publications

Methotrexate Restores CD73 Expression on Th1.17 in Rheumatoid Arthritis and Psoriatic Arthritis Patients and May Contribute to Its Anti-Inflammatory Effect through Ado Production.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets