The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
Semin Arthritis Rheum. 2019 Jun;48(6):1146-1150. doi: 10.1016/j.semarthrit.2019.04.007. Epub 2019 Apr 25.
Systemic lupus erythematosus (SLE) is a representative autoimmune disease characterized by multiple organ manifestations but is molecularly and genetically heterogeneous which makes difficult to manage every case based on one kinetic molecular theory. We, therefore, have tried to obtain a broader perspective on the molecular heterogeneity in SLE by immunophenotyping and found that patients with active SLE can be divided into 3 subgroups based on T cell heterogeneity. Although immunophenotypic features were different even among patients with similar clinical features, patients resistant to treatment were most frequently seen in the follicular helper T cell-dominant group. Because belimumab is only approved targeted therapy for SLE, the concept was encompassed with psoriatic arthritis (PsA) for which multiple biologics are approved. The obtained results suggest the potential for precision medicine via the strategic selection of different biologics based on the phenotypic differences in peripheral helper T cells in individual patients with PsA. Thus, subgrouping heterogeneous diseases could provide good bases for precision medicine, which would encourage treatment strategies of diseases with high clinical and molecular heterogeneity such as SLE.
系统性红斑狼疮(SLE)是一种具有代表性的自身免疫性疾病,其特征为多器官表现,但分子和遗传上存在异质性,这使得基于一种动力学分子理论来管理每个病例变得困难。因此,我们试图通过免疫表型分析获得对 SLE 分子异质性的更广泛视角,并发现根据 T 细胞异质性,活动期 SLE 患者可分为 3 个亚组。尽管即使在具有相似临床特征的患者中,免疫表型特征也不同,但在滤泡辅助 T 细胞占优势的组中最常出现治疗抵抗的患者。因为贝利尤单抗仅被批准用于治疗 SLE,所以该概念被纳入了已批准多种生物制剂的银屑病关节炎(PsA)。这些结果表明,通过基于个体患者外周辅助 T 细胞的表型差异,战略性选择不同的生物制剂,有可能实现精准医学。因此,对异质性疾病进行亚组化可以为精准医学提供良好的基础,这将鼓励治疗具有高临床和分子异质性的疾病,如 SLE。