TNF-α 抑制剂治疗可以改善强直性脊柱炎患者 CD4+T 细胞和负性调节细胞的免疫失衡，但不能改善 CD8+T 细胞的免疫失衡。
TNF-α inhibitor therapy can improve the immune imbalance of CD4+ T cells and negative regulatory cells but not CD8+ T cells in ankylosing spondylitis.
机构信息
Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, Guangdong, China.
出版信息
Arthritis Res Ther. 2020 Jun 19;22(1):149. doi: 10.1186/s13075-020-02226-8.
BACKGROUND
Studies into ankylosing spondylitis (AS) and its relationship with immune imbalance are controversial, and the correlation between the efficacy of TNF-α inhibitor and changes in immune imbalance is unclear.
METHODS
A total of 40 immune cells were tested with flow cytometry, and the results of 105 healthy control (HC) subjects, 177 active-stage AS patients, and 23 AS cases before and after 12 weeks of TNF-α inhibitor therapy (Anbainuo) were analyzed.
RESULTS
Compared with the HC group, the proportion of immune cells, such as naïve and central memory CD4+T cells, in AS increased (P < 0.0001), but effector memory and terminally differentiated CD4+T cells were decreased (P < 0.01 and 0.0001, respectively). Naïve, central memory, and effector memory CD8+T cells were increased (P < 0.0001, 0.001, and 0.01, respectively), but terminally differentiated CD8+T cells were decreased (P < 0.0001). Th1 cells (helper T cells-1), Tfh1 cells (follicular helper T cells-1), Tc1 cells (cytotoxic T cells-1), and Tregs (regulatory T cells) were lower (P < 0.01, 0.05, 0.0001, and 0.001, respectively), but Th17 cells, Tfh17 cells, and Tc cells were higher (P < 0.001, 0.0001, and 0.001, respectively). The proportions of total B cells and class-switched B cells were increased (P < 0.05), but non-switched B cells, plasma cells, memory B cells, and immature Bregs (regulatory B cells) were lower (P < 0.01, 0.0001, 0.0001, and 0.0001, respectively). After Anbainuo therapy, the percentage of naïve CD4+ T cells had decreased (P < 0.05) but Tregs and B10 cells (IL-10-producing regulatory B cells) had increased (P < 0.01 and 0.05, respectively), and the increase in Tregs was positively correlated with the decrease in C-reactive protein (CRP) (r = 0.489, P = 0.018).
CONCLUSIONS
We found that active-stage AS patients have an immunity imbalance of frequency involving multiple types of immune cells, including CD4+T cells, CD8+T cells, Th cells, Tfh cells, Tc cells, Tregs, Bregs, and B cells. TNF-α inhibitor Anbainuo can not only help to inhibit disease activity but can also improve the immune imbalance of CD4+ T cells and negative regulatory cells in frequency. But CD8+ T cells have not been rescued.
背景
强直性脊柱炎（AS）及其与免疫失衡的关系的研究存在争议，且 TNF-α 抑制剂疗效与免疫失衡变化的相关性尚不清楚。
方法
采用流式细胞术检测了 40 种免疫细胞，分析了 105 名健康对照（HC）受试者、177 例活动期 AS 患者和 23 例接受 TNF-α 抑制剂（安百诺）治疗 12 周前后的结果。
结果
与 HC 组相比，AS 患者的免疫细胞比例（如 naïve 和中央记忆 CD4+T 细胞）增加（P<0.0001），但效应记忆和终末分化 CD4+T 细胞减少（P<0.01 和 0.0001，分别）。naïve、中央记忆和效应记忆 CD8+T 细胞增加（P<0.0001、0.001 和 0.01，分别），但终末分化 CD8+T 细胞减少（P<0.0001）。Th1 细胞（辅助 T 细胞-1）、Tfh1 细胞（滤泡辅助 T 细胞-1）、Tc1 细胞（细胞毒性 T 细胞-1）和 Tregs（调节性 T 细胞）降低（P<0.01、0.05、0.0001 和 0.001，分别），但 Th17 细胞、Tfh17 细胞和 Tc 细胞升高（P<0.001、0.0001 和 0.001，分别）。总 B 细胞和类别转换 B 细胞的比例增加（P<0.05），但未转换 B 细胞、浆细胞、记忆 B 细胞和不成熟 Bregs（调节性 B 细胞）降低（P<0.01、0.0001、0.0001 和 0.0001，分别）。安百诺治疗后，naïve CD4+T 细胞的百分比降低（P<0.05），但 Tregs 和 B10 细胞（产生 IL-10 的调节性 B 细胞）增加（P<0.01 和 0.05，分别），Tregs 的增加与 C 反应蛋白（CRP）的降低呈正相关（r=0.489，P=0.018）。
结论
我们发现活动期 AS 患者存在涉及多种类型免疫细胞（包括 CD4+T 细胞、CD8+T 细胞、Th 细胞、Tfh 细胞、Tc 细胞、Tregs、Bregs 和 B 细胞）的频率免疫失衡。TNF-α 抑制剂安百诺不仅有助于抑制疾病活动，还可以改善 CD4+T 细胞和频率负性调节细胞的免疫失衡。但 CD8+T 细胞未得到挽救。
Zotero 插件