Objectives: Th1.17 are highly polyfunctional, potentially harmful CD4+ 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. 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.
This clinical practice study aimed to determine whether the results of systematic US in patients with knee pain modified the rheumatologist's choices concerning diagnostic management and therapy. Patients consulting for non-traumatic knee pain, with recent radiography of the knee, were consecutively included over 9 months. After the radio-clinical assessment, the rheumatologist made a principal diagnosis concerning the knee pain and defined the therapeutic management and a complementary imaging strategy if necessary. US of the painful knee was then done in accordance with the reference protocol with the operators blinded to the clinical results. After reading the US report, the rheumatologist re-evaluated his/her diagnostic and therapeutic approach and the complementary exploration strategy. In the 100 patients included (mean age = 62.9 ± 18.5 years, duration of knee pain = 14.4 ± 8.1 months) with a majority of knee osteoarthritis (61 %), the diagnosis was clarified or modified after the US in 31 % of cases (calcium pyrophosphate deposition arthropathy and tendinitis principally), which led to an intensification of therapy in 15 % of cases and a de-escalation in 5 % of cases. These changes mainly concerned injectable treatments. The US of the painful knee resulted in few changes in imaging prescriptions (6 %), and this was not significant for the number of MRIs requested. In real-life practice in rheumatology, systematic US of the knee clarified the initial clinical diagnosis in almost one-third of cases, but did not significantly modify the therapeutic management, which remained symptomatic, and did not reduce the number of other imaging examinations after the initial radio-clinical assessment.
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