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

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.

Increased proportions of inflammatory T cells and their correlations with cytokines and clinical parameters in patients with ankylosing spondylitis from northern Sweden

“…Additionally, it has been demonstrated that Th22 and IL‐10 show an inverse correlation with the development of Tregs, including immune responses in the gut, highlighting the intricate crosstalk between all of these subsets and the environment 41 . In line with this a decrease of Tregs in AS patients has been demonstrated by several studies and was recently supported by a meta‐analysis of these findings 42 …”

“…41 In line with this a decrease of Tregs in AS patients has been demonstrated by several studies and was recently supported by a metaanalysis of these findings. 42 It has been proposed that microbial dysbiosis, as one key initiating factor in AS, including IL-23 production by gut epithelial cells, may contribute to Th17 and Th22 differentiation and dysfunctional IL-10-mediated regulation. Additionally, the strong contribution of HLA-B27 to AS development has recently been attributed to protein misfolding in antigen-presenting cells, leading to autophagy and subsequent IL-23 production.…”

Single‐cell RNA‐seq reveals altered NK cell subsets and reduced levels of cytotoxic molecules in patients with ankylosing spondylitis

“… 7 Imbalance of immune cell populations is also thought to be a hallmark of AS. 8 Previous studies have shown that the proportion of CD4 lineage T cell subsets, such as Th17 and Th22, that secrete inflammatory cytokines is elevated in the peripheral circulation of AS patients. 9 , 10 In another line of research, some scholars linked AS to the changes in cytotoxic cell profiles.…”

Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury

“… 102 Th17 cells are pro-inflammatory and essential to protect against pathogens by recruitment of neutrophil granulocytes. 103 This cell type plays a determinant role in various inflammatory diseases, including multiple sclerosis, ankylosing spondylitis, inflammatory bowel disease, and rheumatoid arthritis, as well as SCI. 104 , 105 In contrast, Treg are characterized by the specific transcription factor Foxp3 and play a significant role in inhibiting immune response-related neuroinflammation by secreting anti-inflammatory cytokines such as TGF-β and IL-10.…”