Circulating IFN-gamma producing CD4+T cells and IL-17A producing CD4+T cells, HLA-shared epitope and ACPA may characterize the clinical response to therapy in rheumatoid arthritis patients

摘要

This study analyzed the association between peripheral distributions of helper T cell subsets, HLA shared-epitope (SE), anti-cyclic citrullinated peptide antibody (ACPA) and clinical response to therapy in rheumatoid arthritis (RA) patients. Frequencies of IFN-gamma-producing CD4(+)T (Th1) and IL-17A-producing CD4+T (Th17) cells were determined by flow cytometry in 167 patients (114 cases with good-response (GR) and 53 poor-response (PR) based on DAS28). HLA-DRB1 alleles for patients and 150 healthy controls were determined by PCR-SSP. We observed that 65.2% of RA patients were SE+, 63.4%ACPA(+), 43.7%SE(+)ACPA(+) and 14.9% were SE(-)ACPA(-). Higher significantly proportions of Th1 and Th17 cells were found in RA patients than controls (P < 0.05) as well as in the SE+ or ACPA(+)RA patients compared to SE- and ACPA(-) patients. Increased frequencies of both Th subsets were found in SE(+)ACPA(+) versus SE(-)ACPA(-) patients (P < 0.001) and in the PR versus GR group (P < 0.001). We showed significant differences for Th cells frequencies between SE+ and SE- patients in both groups, and between ACPA(+) and ACPA(-) cases in the PR group. Our findings suggest a close link between Th1 and Th17 cells proportions and HLA-SE/ACPA in the RA patients and remarkably in the PR group which could be indicative for the importance of immune monitoring for evaluation of response to therapy.