Abstract
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.
Highlights
Ankylosing spondylitis belong to the group of diseases known as spondyloarthrpathies, which is a spectrum of diseases encompassing psoriatic arthritis, reactive arthritis and undifferentiated spondyloarthritis [1]
Results of the sensitivity analyses can be found in the Supplemental Material 2. This is the first meta-analysis to systemically examine the skewing of functional subgroups of lymphocytes, encompassing the major lymphocyte subsets, namely T cells, B cells, NK cells and NKT cells
Previous meta-analyses done by Li et al and Lai et al focused on regulatory T cells, arriving at the conclusion that the proportions of Tregs are significantly lower in both PBMCs and CD4+ T cells in patients with AS, though the markers used to define Tregs may have an impact on the proportions of Tregs [113, 114]
Summary
Ankylosing spondylitis belong to the group of diseases known as spondyloarthrpathies, which is a spectrum of diseases encompassing psoriatic arthritis, reactive arthritis and undifferentiated spondyloarthritis [1]. Clinical manifestations of ankylosing spondylitis include articular manifestations and extra-articular manifestions. Unlike autoimmune diseases like systemic lupus erythematosus and rheumatoid arthritis, it is not the autoreactive B cells secreting autoantibodies that should be held accountable, since no antibody is widely acknowledged to be detected in patients with ankylosing spondylitis [11]. Instead, such disturbances in the immune system in patients with AS are the result of complicated interactions between the innate immune system and the adaptive immune systems [10]. The hyperactivation of the Th1 effector T cell lineage may secrete abundant IFNg and TNF-a [18], leading to the chronic inflammatory state of the disease
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