Increased circulating CD39+FoxP3+CD4+ regulatory T cells in Early Rheumatoid Arthritis facilitate the antiinflammatory action of methotrexate and associate with the clinical response

Abstract

OBJECTIVESFoxP3+ regulatory T cells (Tregs) are key to the immune system homeostasis; their CD39+ subset (Treg39+) hydrolises adenine nucleotides released by stressed cells, rendering the antiinflammatory adenosine. Methotrexate (MTX), inhibiting AICAR transformylase (ATIC), enhances the extrusion of adenine nucleotides and hence may help Treg39+ cells control inflammation. Therefore, we examined the relation of CD39 expression on Tregs of early RA (ERA) patients with the effect of MTX. METHODSFreshly isolated lymphocytes from 72 untreated ERA patients (duration 39.3 associated with a good 12 month EULAR response [RR 13.4 (2.9-75.6)]. At 12 months, the ERA Treg39+ frequency had decreased to HC levels but its association with the clinical response remained. CONCLUSIONMTX cooperates with Treg39+ cells and the basal Treg39+ frequency is a predictor of clinical response. The increased circulating Treg39+ cells in untreated ERA would further facilitate the action of MTX thereby providing a slot for prompt MTX initiation.