影响利妥昔单抗治疗原发性膜性肾病效果的因素及其机制研究进展

Research advances of factors and mechanisms for therapeutic efficacy of rituximab for primary membranous nephropathy

摘要: 原发性膜性肾病（primary membranous nephropathy，PMN）是由自身抗体介导的肾脏特异性自身免疫病。利妥昔单抗（rituximab，RTX）经过大量临床循证被指南推荐为PMN的一线治疗药物，但仍有20%～40%患者应用RTX未能达到临床缓解。PMN患者疾病活动度高、肾脏损伤重、RTX生物利用度低等临床因素可能与RTX治疗反应不佳有关，组织间隙B细胞残留、CD20阴性B细胞存在、抗原表位扩展、T细胞及其细胞因子紊乱可能是影响RTX疗效的潜在机制，阐明这些临床因素和潜在机制有助于探索改善RTX治疗PMN的疗效。

Abstract: Primary membranous nephropathy （PMN） is a kidney-specific autoimmune disease mediated by autoantibodies. Although rituximab （RTX） has been widely applied as a first-line treatment for PMN, 20%-40% patients are non-responsive to RTX. High disease activity, severe renal lesions and low RTX bioavailability may be correlated with poor therapeutic response to RTX. Residual B cells in tissues, preservation of CD20 negative B cells, epitopic spreading, disorders of T cells and cytokines are potential mechanisms of RTX-refractory PMN. Elucidation of these factors and potential mechanisms shall help to boost the efficacy of RTX for PMN.