The absolute number of circulating Treg cells is reduced in difficult-to-treat RA patients and is ameliorated by low-dose IL-2.

Objective: Circulating regulatory T cells (Tregs) are closely related to immune tolerance and maintenance of immune homeostasis. Perhaps, there is a unique immune cell phenotype for difficult-to-treat rheumatoid arthritis (D2T RA). Low-dose interleukin-2 (IL-2) has been considered for the treatment of autoimmune diseases. This study focused on the uniqueness of D2T RA lymphocyte subsets and the feasibility of low-dose IL-2 therapy. Methods: Participants included 1,042 RA patients who were divided into three groups according to the presence or absence of treatment and their response to treatment in the last 6 months-new group, treated group, and D2T group-and 339 healthy controls (HCs). A total of 381 patients-107, 151, and 123 in each of the three experimental groups-received low-dose IL-2 treatment [0.5 million international units (MIU) per day, subcutaneous injection from day 1 to day 5]. The absolute numbers of peripheral blood lymphocyte subsets were detected by flow cytometry (FCM) and serum cytokine levels were detected by flow cytometry bead array (CBA). Results: The absolute number of T, CD4 Conclusions: The number of lymphocytes and subsets in D2T RA patients was reduced, especially Treg cells, resulting in a shift in the balance of effector T cells/Treg cells toward effector T cells, which is ameliorated by low-dose IL-2 without obvious side effects.