The status of peripheral CD4 + T subsets in patients with rheumatism and their changes after immuno-modulatory combination therapies / 中华风湿病学杂志

ABSTRACT

Objective:To examinethe absolute numbers of cluster of differentiation (CD4) + T cell subsets in peripheral blood of patients with rheumatism and further to develop a new immunomodulatory therapies which aimed to restore their imbalanced CD4 + T lymphocyte subpopulation. Methods:A total of 6 395 rheumatic patients [4 430 females, 1 965 males, mean age (49±15) years] and 206 healthy controls (HCs) were enrolled in this retrospective cross-sectional study, which included rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), Psoriatic arthritis (PsA), systemic sclerosis (SSc), primary Sj?gren′s syndrome (pSS), Be?het's disease (BD), dermatomyositis/polymyositis (DM/PM), gout and vasculitis. Some patients received treatment combined with immunoregulatory drugs (IMiDs) such as low-dose interleukin (IL)-2, rapamycin, metformin, retinoic acid and coenzyme Q10. The absolute numbers of T helper cell (Th)1, Th2, Th17 and regulatory T cell (Treg) in peripheral blood (PB) of these individuals were measured by Flow Cytometery (FCM). Independent sample t test and paired sample t test were used to compare the levels of CD4 + T cell subsets in PB of patients and HCs, before and after treatment respectively, and P<0.05 was considered statistically significant. Results:Compared with HCs, the mean absolute number of Treg was significantly decreased [(31±15) cell/μl vs (27±17) cell/μl, t=3.407, P<0.01] and the ratio of Th17/Treg was increased in all patients [(0.3±0.2) vs ( 0.4±0.7), t=-9.508, P<0.01]. There was a significant increase in the number of Th17 in patients with AS [(10±8) cell/μl, t=-5.403, P<0.01], PsA[ (11±11) cell/μl, t=-3.829, P<0.01], SSc [(7±6) cell/μl, t=3.114, P<0.01], BD [(11±9) cell/μl), t=-4.774, P<0.01] and gout [(11±9) cell/μl, t= -4.604, P<0.01) , and we observed lower level of Treg in patients with RA[(28±15) cell/μl, t=3.032, P<0.01], SLE [(21±21) cell/μl, t=6.836, P<0.01], AS [(28±15) cell/μl, t=2.216, P<0.05], SSc [(27±16) cell/μl, t=3.698, P<0.05], BD [(27±17) cell/μl, t=2.502, P<0.05], DM/PM [(27±22) cell/μl, t=2.974, P<0.01) and gout [(28±15) cell/μl, t=2.079, P<0.05). After IMiDs combination treatment, the levels of CD4 + T subsets were increased. Interestingly, the expansion of Treg was much more dramatical than those of other effector T cells, resulting in a decrease in ratios of Th17/Treg, especially in SLE [(0.6±1.0) vs (0.5±0.4), t=3.157 , P<0.01]. Conclusion:Impaired balance of pro- and anti-inflammatory immune cells, especially insufficiency of Treg, might be a cornerstone of the pathogenesis of rheumatism. The new immunomodulatory therapies could relatively specifically promote Treg proliferation and restored patients' autoimmune tolerance, which isexpected to provide a new strategy for the treatment of rheumatism.