Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China.
Division of Nephrology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China; Division of Nephrology, Department of Medicine, Shenzhen Baoan Shiyan People's Hospital, Shenzhen, Guangdong 518005, China.
Mol Immunol. 2022 Jul;147:90-100. doi: 10.1016/j.molimm.2022.04.006. Epub 2022 May 3.
Primary Sjögren's syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands. The current study was performed to investigate the roles of follicular helper T (Tfh) and follicular regulatory T (Tfr) subsets in patients with pSS, and to evaluate the effects of sirolimus on these cells.
Levels of circulating Tfh and Tfr subsets in 58 pSS patients and 26 healthy controls (HC) were determined by flow cytometry. These T cell subsets were also analyzed in 12 patients before and after treatment with sirolimus. Clinical features and correlations with follicular T cells were analyzed systematically. The discriminative ability of the cells and ratios was evaluated based on the area under the receiver operating characteristic curves.
Patients with pSS had higher percentage and absolute number of PD-1+ICOS+Tfh cells, while lower percentage and absolute number of Tfr, activated regulatory T (aTreg) cells, and CD45RA-Foxp3 activated Tfr cells. Furthermore, increased number of PD-1+ICOS+Tfh cells was associated with B cells, while decreased numbers of Tfr and their subsets was strongly associated with aTreg cells in pSS patients. Also, the higher proportion of PD-1+ICOS+Tfh cells was positively correlated with higher level of autoantibodies, ESR, IgG, cytokines (IL-2, IL-4, IL-10, IL-17, IFN-γ, TNF-α, IL-21 and sIL-2αR), and disease activity. Unexpectedly, the elevated PD-1+ICOS+Tfh:CD45RA-Foxp3 activated Tfr ratio had the greatest ability to discriminate between pSS and HC, and sirolimus therapy restored the PD-1+ICOS+Tfh cells:CD45RA-Foxp3 activated Tfr ratio, and controlled disease activity.
The novel ratio of PD-1+ICOS+Tfh to CD45RA-Foxp3 activated Tfr cells can effectively discriminate the pSS patients from controls, and Tfr cell subsets may resemble Treg cell lineages. Furthermore, the PD-1+ICOS+Tfh cells can be used as a biomarker of disease activity and to verify the therapeutic effects of sirolimus in pSS.
原发性干燥综合征（pSS）是一种常见的慢性自身免疫性疾病，其特征为唾液腺和泪腺的淋巴细胞浸润。本研究旨在探讨滤泡辅助 T（Tfh）和滤泡调节性 T（Tfr）亚群在 pSS 患者中的作用，并评估西罗莫司对这些细胞的影响。
采用流式细胞术检测 58 例 pSS 患者和 26 例健康对照者（HC）外周血循环 Tfh 和 Tfr 亚群水平。分析了 12 例患者在接受西罗莫司治疗前后的 T 细胞亚群。系统分析了临床特征与滤泡 T 细胞的相关性。根据受试者工作特征曲线下面积评估细胞和比值的鉴别能力。
pSS 患者 PD-1+ICOS+Tfh 细胞的百分比和绝对数较高，而 Tfr、活化调节性 T（aTreg）细胞和 CD45RA-Foxp3 活化 Tfr 细胞的百分比和绝对数较低。此外，pSS 患者中，PD-1+ICOS+Tfh 细胞数量的增加与 B 细胞有关，而 Tfr 及其亚群数量的减少与 aTreg 细胞密切相关。此外，较高比例的 PD-1+ICOS+Tfh 细胞与自身抗体、ESR、IgG、细胞因子（IL-2、IL-4、IL-10、IL-17、IFN-γ、TNF-α、IL-21 和 sIL-2αR）水平和疾病活动度呈正相关。出乎意料的是，升高的 PD-1+ICOS+Tfh：CD45RA-Foxp3 活化 Tfr 比值具有最强的鉴别 pSS 与 HC 的能力，而西罗莫司治疗恢复了 PD-1+ICOS+Tfh 细胞：CD45RA-Foxp3 活化 Tfr 比值，并控制了疾病活动度。
新型 PD-1+ICOS+Tfh 与 CD45RA-Foxp3 活化 Tfr 细胞比值可有效鉴别 pSS 患者与对照者，Tfr 细胞亚群可能类似于 Treg 细胞系。此外，PD-1+ICOS+Tfh 细胞可作为疾病活动的生物标志物，并验证西罗莫司治疗 pSS 的疗效。
