Abstract
Studies on the number and proportion of regulatory T cells (Tregs) in ankylosing spondylitis (AS) patients have been controversial, which has led to a disagreement regarding the role of Tregs in the pathogenesis of AS. To clarify this debate, we conducted a meta-analysis to verify the reported changes in Tregs during AS. We systematically searched the PubMed, Foreign Medical Retrieval System (FMRS), and China National Knowledge Infrastructure (CNKI) web of knowledge databases for eligible articles. A meta-analysis of studies that examined the proportion and number of Tregs among peripheral blood mononuclear cells (PBMCs) and CD4+ T cells was performed using Stata software. Further, subgroup analysis was performed based on Treg definition markers and disease activity to identify potential sources of heterogeneity. Forty-seven studies involving a total of 4373 participants were included in the meta-analysis. The Treg/PBMC and Treg/CD4+ T cell ratios were significantly lower in AS patients than those in healthy controls (HCs). A subgroup analysis indicated that patients defined by CD4+CD25+/high, CD4+CD25+CD127low/−, and CD4+CD25+FOXP3+ had much lower Treg/PBMC and Treg/CD4+ T cell ratios than HCs. Active AS patients also had a substantially lower proportion of Tregs/PBMCs and Treg/CD4+ T cells than HCs. The proportion of Tregs among both PBMCs and CD4+ T cells was significantly decreased in AS patients. Treg definition markers and disease activity may influence the proportion of Tregs measured among the PBMC and CD4+ T cell populations. Further study of the correlation between AS disease activity and the proportion of Tregs in peripheral blood is needed to determine the physiological role of this association. This study implies that loss of Tregs may play a role in the pathogenesis of AS and helps clarify the contradictory Treg results in AS patients. This trial is registered with PROSPERO (CRD42019147064).
Highlights
Ankylosing spondylitis (AS) is a chronic, inflammatory, systemic immune disease, which is characterized by inflammation of the spine and the sacroiliac joints
A growing body of evidence suggests that functional defects in Tregs are present in patients with AS and suggests that this may be due to defects in IL-2, decreased phosphorylation of STAT5, decreased expression of fork box P3 (FOXP3)+, and elevated levels of CpG methylation in the CNS2 region of the FOXP3 gene
Inclusion Criteria. e following criteria were used to determine if a search result was included in the analysis: (a) original research, (b) human research, (c) the terms “ankylosing spondylitis” and “regulatory T” included in the title or abstract, (d) studies that report the proportion of Tregs in CD4+ T cells or peripheral blood of AS patients, and (e) studies that can be found on the Internet; the manuscript is linked from the search site to the full text of the manuscript (PDF or website)
Summary
Ankylosing spondylitis (AS) is a chronic, inflammatory, systemic immune disease, which is characterized by inflammation of the spine and the sacroiliac joints. Treg cells do not control the proliferation of effector CD4+ T cells [7, 8], and activation of Tregs has been used to treat AS [9, 10]. Despite this evidence, we have less confidence in the possible beneficial effects of therapeutic Tregs in AS patients. BioMed Research International of Tregs in patients with ankylosing spondylitis, but the results were not consistent; a reduction [11,12,13], elevation [8, 14, 15], and no significant change [16, 17] in the number of Tregs in AS patients have all been reported. Understanding changes in the number of Tregs during AS will help us understand the role of Tregs in the pathogenesis of AS in more detail
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