Altered follicular regulatory T (Tfr)- and helper T (Tfh)-cell subsets are associated with autoantibody levels in microscopic polyangiitis patients
Altered follicular regulatory T (Tfr)- and helper T (Tfh)-cell subsets are associated with autoantibody levels in microscopic polyangiitis patients
复制标题
滤泡调节性 T (Tfr) 和辅助性 T (Tfh) 细胞亚群的改变与显微镜下多血管炎患者的自身抗体水平相关
DOI：
10.1002/eji.202049093
复制
发表时间：
2021-04-23
影响因子：
5.4
通讯作者：
Liu, Chen
中科院分区：
文献类型：
--
作者：
Long, Yan;Feng, Jinghong;Liu, Chen
抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）是一种以B细胞来源的ANCA为特征的自身免疫性疾病，且ANCA已被证实是其发病机制中的关键因素。滤泡调节性T（Tfr）细胞和滤泡辅助性T（Tfh）细胞是T细胞亚群，在B细胞成熟和抗体产生过程中发挥重要作用。然而，它们在显微镜下多血管炎（MPA，AAV的一种类型）患者中的意义尚未得到深入研究。在本研究中，对MPA患者和健康对照者（HCs）的循环Tfr和Tfh细胞进行了综合模式分析，我们发现MPA患者的Tfr水平和Tfr/Tfh比值显著降低。与HCs相比，MPA患者中Helios +、CD45RA - FoxP3hi和Ki - 67 + Tfr细胞较少，而CD226 + Tfr细胞较多。这些表型表明Tfr细胞的功能和增殖能力相对受损。包括ICOS + PD - 1 +和Ki - 67 + Tfh在内的Tfh亚群显著增加，这表明尽管MPA患者的总Tfh水平没有显著变化，但Tfh的功能有所增强。MPA患者循环记忆B细胞和浆母细胞显著升高，且与Tfr水平和Tfr/Tfh比值呈负相关。此外，Tfr水平和Tfr/Tfh比值与血清髓过氧化物酶（MPO） - ANCA水平呈负相关，而Tfh与之呈正相关。再者，Tfr和Tfr/Tfh比值也与血肌酐（SCr）、尿素氮（BUN）、白细胞介素 - 4（IL - 4）和白细胞介素 - 21（IL - 21）水平呈负相关。我们的研究结果表明，Tfr和Tfh功能亚群的失衡与MPA患者自身抗体水平升高有关，我们提出了MPA发病机制的一种新机制。
Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is an autoimmune disease characterized by B cells-derived ANCAs, and ANCA was proved to be a key factor in its pathogenesis. Follicular regulatory T (Tfr) and follicular helper T (Tfh) cells were T-cell subsets that play important roles in B-cell maturation and antibody production. However, their significances in microscopic polyangiitis (MPA) patients, one type of AAV, has not been thoroughly studied. In this study, comprehensive pattern analyses of circulating Tfr and Tfh were performed in MPA patients and healthy controls (HCs), and we found Tfr levels and Tfr/Tfh ratios were significantly decreased in MPA patients. Compared with HCs, Helios+, CD45RA-FoxP3hi, and Ki-67+ Tfr were lower in MPA patients, while CD226+ Tfr cells were higher. These phenotypes suggest that function and proliferation ability of Tfr cells were relatively impaired. Tfh subsets, including ICOS+PD-1+ and Ki-67+ Tfh, were significantly increased, suggesting that the function of Tfh was enhanced in MPA although the total Tfh levels did not change significantly. Circulating memory B cells and plasmablasts were significantly elevated and negatively correlated with Tfr levels and Tfr/Tfh ratios in MPA patients. In addition, Tfr levels and Tfr/Tfh ratios were negatively while Tfh was positively correlated with serum myeloperoxidase (MPO)-ANCA levels. Furthermore, Tfr and Tfr/Tfh ratio were also reversely associated with SCr, BUN, IL-4, and IL-21 levels. Our results suggest that the imbalance of Tfr and Tfh functional subsets is related to increased level of autoantibodies in MPA patients, and we propose a new mechanism for the pathogenesis of MPA.