Renal Diseases Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
Assistance Publique des Hôpitaux de Paris, Hôpitaux Universitaires Henri-Mondor, Service de Néphrologie et Transplantation, Centre de Référence Maladie Rare "Syndrome Néphrotique Idiopathique", Fédération Hospitalo-Universitaire, Innovative Therapy for Immune Disorders, Créteil, France.
Front Immunol. 2022 Jan 24;13:823204. doi: 10.3389/fimmu.2022.823204. eCollection 2022.
The therapeutic efficacy of B-cell depletion by anti-CD20 treatment in pediatric and, more recently, in adult idiopathic nephrotic syndrome patients suggests a key role of B cells in the pathogenesis of the disease. However, their exact role is still unclear. B cells are able to secrete a large variety of antibodies that can protect against infections. However, B-cell dysregulation is well-established in a variety of autoimmune diseases. In parallel with their ability to produce antibodies, pathogenic B cells display altered effector functions by expressing activating surface molecules, which can strongly modify the immune homeostasis, or by producing specific cytokines, which can directly affect either podocyte structure and functions or modulate T-cell homeostasis. Herein, we report the most relevant clinical and experimental evidences of a pathogenic role of B cells in idiopathic nephrotic syndrome. We further highlight similarities and differences between children and adults affected by non-genetic forms of the disease and discuss what needs to be investigated in order to define the exact mechanisms underlying the pathogenic role of B cells and to identify more tailored therapeutic approaches.
B 细胞耗竭疗法通过抗 CD20 治疗在儿科和最近在成人特发性肾病综合征患者中的疗效表明 B 细胞在疾病发病机制中起关键作用。然而，它们的确切作用仍不清楚。B 细胞能够分泌大量的抗体，可预防感染。然而，B 细胞失调在多种自身免疫性疾病中已得到充分证实。与产生抗体的能力并行的是，致病性 B 细胞通过表达激活表面分子而显示出改变的效应功能，这些分子可以强烈改变免疫平衡，或者通过产生特定的细胞因子，这些细胞因子可以直接影响足细胞的结构和功能，或者调节 T 细胞的平衡。在此，我们报告了 B 细胞在特发性肾病综合征中具有致病性作用的最相关的临床和实验证据。我们还进一步强调了受非遗传形式疾病影响的儿童和成人之间的相似性和差异，并讨论了为了确定 B 细胞致病性作用的确切机制以及确定更具针对性的治疗方法，需要研究哪些方面。
