The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan.
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan.
Clin Immunol. 2018 Jan;186:21-25. doi: 10.1016/j.clim.2017.07.010. Epub 2017 Aug 5.
B cells play a pivotal role in the initiation and perpetuation of SLE. Because SLE is molecularly and clinically heterogeneous, efficacious targeted therapy to clinical remission has not yet been established in SLE. We have found i) statistical clustering between Tfh cells and class-switched memory B cells and the upregulated transition from CXCR5 IgM memory B cells to CXCR3 class-switched memory B cells in SLE by 8-color flow cytometry, ii) the involvement of Syk, Btk and JAK in the activation and differentiation of B cells in SLE, iii) SLE patients was divided to 3 groups based on immunophenotypic analysis and statistical analysis and patients in the Tfh/class-switched B cell-dominant group were most refractory to conventional therapies although 3 groups had similar clinical features. Thus, novel therapies targeting Tfh-memory B cell interaction are anticipated in certain subpopulation of SLE patients, which leads to the precision medicine in SLE.
B 细胞在启动和维持 SLE 中起着关键作用。由于 SLE 在分子和临床上具有异质性，因此尚未在 SLE 中建立针对临床缓解的有效靶向治疗。我们发现：i）通过 8 色流式细胞术发现 Tfh 细胞和类别转换记忆 B 细胞之间存在统计学聚类，以及 CXCR5 IgM 记忆 B 细胞向 CXCR3 类别转换记忆 B 细胞的上调转变；ii）在 SLE 中，Syk、Btk 和 JAK 参与 B 细胞的激活和分化；iii）根据免疫表型分析和统计分析，将 SLE 患者分为 3 组，尽管 3 组具有相似的临床特征，但 Tfh/类别转换 B 细胞优势组的患者对常规治疗最具抵抗力。因此，针对 Tfh-记忆 B 细胞相互作用的新型疗法有望在某些 SLE 患者亚群中发挥作用，从而实现 SLE 的精准医疗。
