Peripheral distributions of IL-4-producing CD4 + T cells and CD4 + CD25 + FoxP3 + T cells (Tregs) in rheumatoid arthritis patients with poor response to therapy are associated with HLA shared epitope alleles and ACPA status

Abstract

Specific profiling of CD4 + T cell subsets in the circulation and inflamed joints of rheumatoid arthritis (RA) patients may have therapeutic implications. This study aimed to evaluate the peripheral distributions of Th2 and Treg cells in relation to HLA-shared epitope (SE) alleles and anti-cyclic citrullinated peptide antibody (ACPAs) status in patients with good response (GR) and poor response (PR) to treatment. The frequencies of IL-4-producing CD4 + T cells (Th2) and CD4 + CD25 + Foxp3 + T cells (Tregs) were determined by flow cytometry in 167 RA patients including 114 GR and 53 PR cases. CD4 + T cell subsets were also analyzed based on HLA-SE and ACPAs statuses. One hundred nine of 167 patients were positives for HLA-SE, 63.4 for ACPAs, 43.7 for SE/ACPAs and 14.9 were negatives for SE/ACPAs. Higher frequencies of Th2 (P = 0.001) and Treg cells (P = 0.03) were found in the patients versus controls. Increased and decreased frequencies of Th2 and Tregs cells were observed in the PR versus GR patients respectively (P = 0.003 and P = 0.004). Higher proportions of Th2 cells were observed in the SE(+)RA versus SE(-)RA (P = 0.001), in ACPA(+)RA versus ACPA(-)RA (P = 0.005) and in the SE(+)ACPA(+)RA versus SE(-)ACPA(-)RA patients (P = 0.002). Treg cells frequencies decreased in the SE(+)RA versus SE(-)RA (P = 0.03) and in SE(+)ACPA(+)RA versus SE(-)ACPA(-)RA (P = 0.02). ACPA(+)GR and SE(+)PR patients showed higher proportions of Th2 cells than ACPA(-)GR and SE(-)PR patients respectively (P = 0.02 and P = 0.01). Analysis of the CD4 + T cell subsets profiles in conjunction with genetic background and autoantibodies patterns can be useful for precise therapeutic response monitoring in the RA patients.