强直性脊柱炎患者外周血中循环滤泡辅助性T细胞与抗体分泌B细胞关系的研究

The association between peripheral blood circulating follicular helper T cells and antibody-secreting B cells in patients with ankylosing spondylitis

目的探讨AS患者外周血中循环滤泡辅助性T细胞（cTfh）与抗体分泌B细胞（CD19＋ CD38＋ B）的关系及其在AS发病机制中的作用。方法收集AS患者59例（其中活动组36例，非活动组23例）、健康对照20名，流式细胞术检测研究对象外周血中CD4＋ CXCR5＋ T细胞（cTfh）、CD4＋ CXCR5＋ PD-1＋ T细胞、CD4＋ CXCR5＋ ICOS＋ T细胞、CD19＋ B细胞、CD19＋ CD38＋ B细胞的表达水平；统计学处理采用独立样本t检验,单因素方差分析、Pearson及Spearman相关分析。结果AS患者组外周血cTfh[（26.8±10.4）%]、CD4＋ CXCR5＋ PD-1＋ T细胞[（12.1±14.0）%]、CD4＋ CXCR5＋ ICOS＋ T细胞[（13.6±9.5）%]、CD19＋ CD38＋ B细胞[（80.7±13.0）%]的百分率高于健康对照组[（15.6±4.5）%、（6.4±2.4）%、（9.4±4.5）%、（68.2±13.0）%]（t=6.663，P〈0.01；t=2.999，P〈0.01；t=2.573，P〈0.05；t=2.712，P〈0.01）。AS活动组外周血cTfh细胞的百分率[（30.2±11.0）%]明显高于非活动组[（21.4±6.5）%]及健康对照组（t=3.444，P〈0.01；t=7.004，P〈0.01）；AS活动组外周血CD19＋ CD38＋ B细胞的百分率[（85.1±10.0）%]显著高于AS非活动组[（73.8±14.2）%]及健康对照组（t=3.561，P〈0.01；t=5.410，P〈0.01）；AS患者外周血cTfh、CD19＋ CD38＋ B细胞的表达水平分别与BASDAI呈正相关（r=0.442，P〈0.01；r=0.405，P=0.001），且CD19＋ CD38＋ B细胞的百分率与cTfh的百分率呈正相关（r=0.420，P=0.001）。 结论AS患者外周血CD4＋ CXCR5＋ T（cTfh）细胞水平显著升高，伴随抗体分泌B细胞（CD19＋ CD38＋ B）比例增加，提示cTfh细胞与抗体分泌B细胞可能在AS发病机制中发挥重要作用。

ObjectiveTo investigate the relationship between peripheral blood circulating follicular helper T cells and antibody-secreting B cells in patients with ankylosing spondylitis （AS）. The role of circulating follicular helper T cells and antibody-secreting B cells in the pathogenesis of AS were explored.MethodsFlow cytometry was used to detect the levels of peripheral blood CD4＋CXCR5＋ T（cTfh）, CD4＋CXCR5＋ PD-1＋ T, CD4＋ CXCR5＋ ICOS＋ T, CD19＋ B, CD19＋ CD38＋ B cells in 59 patients with AS （including 36 cases of active AS patients and 23 cases of inactive AS patients）. In addition, twenty healthy persons were selected as the controls. Data analysis were performed by independent-sample t test, One way ANOVA analysis, Pearson＇s and Spearman＇s correlation test.ResultsThe percentages of cTfh[（26.8±10.4）%], CD4＋CXCR5＋ PD-1＋ T [（12.1±14.0）%], CD4＋CXCR5＋ICOS＋ T [（13.6±9.5）%], CD19＋CD38＋ B [（80.7±13.0）%] in the peripheral blood of AS group were significantly higher than healthy controls [（15.6±4.5）%, （6.4±2.4）%, （9.4±4.5）%, （68.2±13.0）%] （t=6.663, P〈0.01; t=2.999, P〈0.01; t=2.573, P〈0.05; t=2.712, P〈0.01） . The percentages of cTfh in the active AS group [（30.2±11.0）%] were significantly higher than those in the inactive AS group [（21.4±6.5）%] and HC （t=3.444, P〈0.01; t=7.004, P〈0.01）. The percentage of CD19＋ CD38＋ B [（85.1±10.0）%] in the peripheral blood of active AS group was significantly higher than that of the inactive AS group [（73.8±14.2）%] and HC （t=3.561, P〈0.01; t=5.410, P〈0.01）. The relationship between Bath AS disease activity index （BASDAI） and the percentage of cTfh, CD19＋ CD38＋ B was a positive correlation （r=0.442, P〈0.01; r=0.405, P=0.001）, and significant positive correlation was observed between the percentages of cTfh and CD19＋CD38＋ B cells （r=0.420, P=0.001）.ConclusionCD4＋CXCR5＋·cTfh cells are significantly increased in peripheral blood in AS patients with aberrant CD19＋ CD38＋ antibody-secreting B cells, suggesting that cTfh and CD19＋ CD38＋ antibody-secreting B cells may play an important role in the pathogenesis of AS.