Liossis Stamatis-Nick C, Staveri Chrysanthi
Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, Patras, Greece.
Division of Rheumatology, Department of Internal Medicine, University of Patras Medical School, Patras, Greece.
Front Med (Lausanne). 2022 Jul 4;9:936182. doi: 10.3389/fmed.2022.936182. eCollection 2022.
Systemic sclerosis (SSc) is a chronic, autoimmune, multisystem disease characterized by tissue fibrosis that, apart from the skin, may affect the lungs among other organs. B cells have been found in tissue lymphocytic infiltrates; in the lungs are encountered in lymphoid aggregates. The abnormal and hyperreactive B cell in SSc may initiate and perpetuate the fibrotic process via incompletely understood mechanisms. Studies in animal models of SSc have demonstrated that B cell dysregulation is an early event in disease pathogenesis. Functional disturbances of BCR signaling such as decreased inhibitory CD22 signal transduction or augmented CD19-mediated signaling result in prolonged B cell activation. Antagonism of BAFF, a cytokine known for his central role in B cell survival and maturation, not only suppresses the production of fibrogenic cytokines such as IL-6 and IL-10, but also amplifies antifibrogenic cytokine secretion such as IFN-γ and it finally contributes to skin fibrosis attenuation. B cells subsets in SSc patients display several abnormalities. Naïve B cells are increased, in contrast to switched memory B cells that are not only decreased but also activated. Disturbances in the expression of molecules that are involved in B cell tuning have also been described. Interestingly, a distinct B cell population characterized by anergy and exhaustion has been found to be increased in patients with SSc-ILD. Another B cell subset, the CD30GM-Beff, is capable to differentiate monocytes to dendritic cells and is increased in SSc patients with ILD. Of note, patients with SSc-ILD exhibit increased expression of the inhibitory receptor FcγRIIB on naïve and double negative B cells aiming perhaps to counterbalance the abnormal B cell activation. Studies of B cell targeted treatments have demonstrated promising clinical efficacy. Therefore, B cell eliminating therapies could be integrated into the therapeutic armamentarium of patients suffering from SSc-ILD aiming to at least stabilize the fibrotic lung process.
系统性硬化症（SSc）是一种慢性自身免疫性多系统疾病，其特征为组织纤维化，除皮肤外，还可能影响肺部等其他器官。在组织淋巴细胞浸润中发现了B细胞；在肺部的淋巴样聚集体中也可发现。SSc中异常且反应性过高的B细胞可能通过尚不完全清楚的机制启动并维持纤维化过程。在SSc动物模型中的研究表明，B细胞失调是疾病发病机制中的早期事件。BCR信号传导的功能障碍，如抑制性CD22信号转导减少或CD19介导的信号增强，会导致B细胞活化延长。BAFF是一种在B细胞存活和成熟中起核心作用的细胞因子，拮抗它不仅能抑制促纤维化细胞因子如IL-6和IL-10的产生，还能增强抗纤维化细胞因子如IFN-γ的分泌，最终有助于减轻皮肤纤维化。SSc患者的B细胞亚群表现出多种异常。与转换记忆B细胞减少且活化不同，初始B细胞增加。还描述了参与B细胞调节的分子表达紊乱情况。有趣的是，在SSc-ILD患者中发现，以无反应性和耗竭为特征的独特B细胞群体有所增加。另一个B细胞亚群CD30GM-Beff能够将单核细胞分化为树突状细胞，在患有ILD的SSc患者中增加。值得注意的是，SSc-ILD患者的初始B细胞和双阴性B细胞上抑制性受体FcγRIIB的表达增加，这可能是为了平衡异常的B细胞活化。针对B细胞的治疗研究已显示出有前景的临床疗效。因此，B细胞清除疗法可纳入SSc-ILD患者的治疗方案中，旨在至少稳定肺部纤维化进程。
