Imbalance of Peripheral Lymphocyte Subsets in Patients With Ankylosing Spondylitis: A Meta-Analysis

Ankylosing spondylitis is a complicated consequence of genetic predisposition and environmental factors. Enthesitis is believed to be the hallmark of ankylosing spondylitis, and the chronic inflammatory state of this disease is perpetuated by the disturbances of both the innate immune system and the acquired immune system. To clarify the alteration of immune system in patients with AS, we conducted a meta-analysis concerning the proportions of major lymphocyte subsets in the peripheral blood of AS patients. We systematically searched PubMed and China National Knowledge Infrastructure (CNKI) for articles related to this subject. A total of 95 articles involving 4,020 AS patients and 3,065 healthy controls were included in the analysis. This meta-analysis is performed on R platform using R package "meta", and Egger's tests were used to determine the presence of publication bias. Results showed that the percentages of T cells, NK cells and NKT cells were not significantly different between AS patients and healthy controls, but B cells were significantly increased. Among the subsets of T cells, the proportions of CD4+ T cells, Th17 cells, Tfh cells as well as Th1/Th2 ratio were significantly increased, while Tregs were significantly decreased. Subgroup analysis showed that the proportions of Th17 among both PBMCs, T cells and CD4+ T cells were significantly elevated, while Tregs were only significantly lower in PBMCs. Subgroup analysis also demonstrated that Tregs defined by "CD4+CD25+FoxP3+", "CD4+CD25+CD127low"or "CD4+CD25+CD127-"were significantly downregulated, indicating that the selection of markers could be critical. Further study is warranted in order to elucidate the complicated interactions between different lymphocyte subsets in AS patients. This study implied that the disequilibrium between Th17 and Tregs, as well as between Th1 and Th2 could contribute to the pathogenesis of ankylosing spondylitis, further cementing the understanding that ankylosing spondylitis is a consequence of disrupted balance of innate immune system and acquired immune system.