利妥昔单抗在成人微小变化疾病和免疫介导的局灶性和节段性肾小球硬化症治疗中的作用综述。

Glomerular diseases Pub Date : 2023-08-18 eCollection Date: 2023-01-01 DOI:10.1159/000533695
Ahsan Aslam, Abbal Koirala
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引用次数: 0

摘要

背景:微小变化性疾病和原发性FSGS是足细胞病,但也是免疫介导的疾病。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细胞之间的平衡向有利于调节性B和T细胞倾斜。其结果是这些细胞产生的细胞因子、趋化因子和渗透因子减少。在过去的十年里,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UCHL1抗体和抗nephrin抗体),利妥昔单抗降低了它们的产生。利妥昔单抗还与足细胞SMPDL3b结合,并具有直接的足细胞作用。摘要:利妥昔单抗在治疗这些原发性足细胞病中的作用已在本综述中进行了讨论。利妥昔单抗已广泛用于儿童和成人经常复发和类固醇依赖性肾病综合征。然而,利妥昔单抗治疗成人激素抵抗性肾病综合征的前景并不乐观。尽管奥法单抗会导致B细胞长期耗竭,并且是完全人源化的,但尚不清楚它在预防肾病综合征复发方面是否优于利妥昔单抗。关键信息:利妥昔单抗治疗可诱导经常复发和类固醇依赖性肾病综合征的成人长期缓解。然而,目前尚无关于利妥昔单抗治疗激素抵抗性肾病综合征的良好数据。
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Review of the Role of Rituximab in the Management of Adult Minimal Change Disease and Immune-Mediated Focal and Segmental Glomerulosclerosis.

Background: 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.

Summary: 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.

Key messages: 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.

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