{Reference Type}: Journal Article
{Title}: Transiently increased circulating CD39+FoxP3+ Treg cells predict the clinical response to Methotrexate in Early Rheumatoid Arthritis.
{Author}: Villalba A;Nuño L;Benito-Miguel M;Nieto-Carvalhal B;Monjo I;Novella-Navarro M;Peiteado D;García-Carazo S;Balsa A;Miranda-Carús ME;
{Journal}: Rheumatology (Oxford)
{Volume}: 0
{Issue}: 0
{Year}: 2024 Aug 14
{Factor}: 7.046
{DOI}: 10.1093/rheumatology/keae446
{Abstract}: <B>OBJECTIVE: </B>A subset of human circulating FoxP3+ regulatory T cells expresses CD39 (cTreg39+) and hydrolyses pro-inflammatory adenine nucleotides released at inflammatory foci, rendering the anti-inflammatory agent adenosine. Methotrexate (MTX), inhibiting ATIC, enhances the extrusion of adenine nucleotides and may help Treg39+ cells control inflammation. Therefore, we examined the relation of cTreg39+ cells with the effect of MTX in early Rheumatoid Arthritis (eRA).<BR><B>METHODS: </B>Freshly isolated peripheral blood lymphocytes from 98 untreated eRA patients and 98 healthy controls (HC) were examined by cytometry. Twelve months (12m) after initiating MTX, 82 patients were clinically re-evaluated and cytometry was repeated in 40 of them. The effect of MTX on Treg cell potency was assessed in Treg/Tresp cocultures.<BR><B>RESULTS: </B>The baseline (0m) cTreg39+ cell frequency was elevated in eRA above HC levels. Patients who reached low disease activity at 12 months (12m-LDA, DAS28-ESR≤ 3.2, n = 51) had presented with a significantly higher 0m cTreg39+ frequency vs those who did not (n = 31). The 0m cTreg39+ cutoff for attaining 12 m-LDA was 42.0% (Sensitivity=90.4%/Specificity=96.8%). At 12m, the cTreg39+ frequency was no longer elevated but its association with disease activity remained: it was still significantly higher in patients who had reached LDA vs those who had not. In vitro, MTX augmented the Treg39+ cell potency but had no effect on Treg39- cells.<BR><B>CONCLUSIONS: </B>MTX cooperates with Treg39+ cells and the baseline cTreg39+ frequency predicts the response to MTX in eRA. In addition, the transiently elevated baseline cTreg39+ frequency in eRA may provide a slot for prompt MTX initiation.