Liu Dong, Liu Budian, Lin Churong, Gu Jieruo
Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Radiology Department, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Front Immunol. 2021 Jul 6;12:696973. doi: 10.3389/fimmu.2021.696973. eCollection 2021.
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.
强直性脊柱炎是遗传易感性和环境因素共同作用的复杂结果。附着点炎被认为是强直性脊柱炎的标志，并且该疾病的慢性炎症状态通过先天免疫系统和获得性免疫系统的紊乱而持续存在。为了阐明强直性脊柱炎患者免疫系统的变化，我们针对强直性脊柱炎患者外周血中主要淋巴细胞亚群的比例进行了一项荟萃分析。我们系统地检索了PubMed和中国知网（CNKI）中与此主题相关的文章。共有95篇文章纳入分析，涉及4020例强直性脊柱炎患者和3065例健康对照。本荟萃分析在R平台上使用R包“meta”进行，并采用Egger检验来确定发表偏倚的存在。结果显示，强直性脊柱炎患者与健康对照之间T细胞、NK细胞和NKT细胞的百分比无显著差异，但B细胞显著增加。在T细胞亚群中，CD4 + T细胞、Th17细胞、滤泡辅助性T细胞（Tfh细胞）的比例以及Th1/Th2比值显著增加，而调节性T细胞（Tregs）显著减少。亚组分析表明，外周血单个核细胞（PBMCs）、T细胞和CD4 + T细胞中Th17细胞的比例均显著升高，而Tregs仅在外周血单个核细胞中显著降低。亚组分析还表明，由“CD4 + CD25 + FoxP3 +”、“CD4 + CD25 + CD127low”或“CD4 + CD25 + CD127 -”定义的Tregs显著下调，表明标志物的选择可能至关重要。有必要进行进一步研究以阐明强直性脊柱炎患者不同淋巴细胞亚群之间复杂的相互作用。本研究表明，Th17与Tregs之间以及Th1与Th2之间的失衡可能促成强直性脊柱炎的发病机制，进一步巩固了强直性脊柱炎是先天免疫系统和获得性免疫系统平衡破坏的结果这一认识。
