Aslam Ahsan, Koirala Abbal
Division of Nephrology and Hypertension, Assistant Professor of Clinical Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Division of Nephrology, Clinical Assistant Professor of Medicine, University of Washington, Seattle, WA, USA.
Glomerular Dis. 2023 Aug 18;3(1):211-219. doi: 10.1159/000533695. eCollection 2023 Jan-Dec.
Minimal change disease and primary FSGS are podocytopathies but are also immune-mediated diseases. Rituximab acts via multiple mechanisms by tilting the balance between autoreactive B and T cells in favor of regulatory B and T cells. The consequences are decreased production of cytokines, chemokines, and permeability factors by these cells. In the past decade, we have seen the discovery of autoantibodies mediating nephrotic syndrome (anti-annexin A2 antibody, anti-UCHL1 antibody, and anti-nephrin antibody), and rituximab decreases their production. Rituximab also binds to podocyte SMPDL3b and has direct podocyte actions.
Rituximab's role in managing these primary podocytopathies has been discussed in this brief review. Rituximab has been used extensively in children and adults with frequently relapsing and steroid-dependent nephrotic syndrome. However, rituximab is not very promising in adult steroid-resistant nephrotic syndrome. Although ofatumumab would cause prolonged B-cell depletion and is fully humanized, it is unclear if it is superior to rituximab in preventing relapse of nephrotic syndrome.
Rituximab therapy can induce prolonged remission in adults with frequently relapsing and steroid-dependent nephrotic syndrome. However, no good data exist on using rituximab in steroid-resistant nephrotic syndrome.
微小病变病和原发性局灶节段性肾小球硬化症是足细胞病，但也是免疫介导性疾病。利妥昔单抗通过多种机制发挥作用，使自身反应性B细胞和T细胞之间的平衡向调节性B细胞和T细胞倾斜。其结果是这些细胞产生的细胞因子、趋化因子和通透性因子减少。在过去十年中，我们发现了介导肾病综合征的自身抗体（抗膜联蛋白A2抗体、抗泛素羧基末端水解酶L1抗体和抗nephrin抗体），而利妥昔单抗可减少它们的产生。利妥昔单抗还与足细胞的鞘磷脂磷酸二酯酶3b结合并对足细胞有直接作用。
在这篇简短的综述中讨论了利妥昔单抗在治疗这些原发性足细胞病中的作用。利妥昔单抗已广泛用于患有频繁复发和激素依赖型肾病综合征的儿童和成人。然而，利妥昔单抗在成人激素抵抗型肾病综合征中前景不太乐观。虽然奥法木单抗会导致B细胞长期耗竭且是完全人源化的，但在预防肾病综合征复发方面它是否优于利妥昔单抗尚不清楚。
利妥昔单抗治疗可使频繁复发和激素依赖型肾病综合征的成人患者获得长期缓解。然而，在激素抵抗型肾病综合征中使用利妥昔单抗尚无充分的数据。
