Service de néphrologie, IFRNT, Le Kremlin-Bicêtre, France.
Département de Médecine Interne et d'Immunologie clinique, Groupe Hospitalier Pitié-Salpêtrière, 84, boulevard de l'Hôpital, Paris 75013, France.
J Autoimmun. 2015 Jun;60:74-9. doi: 10.1016/j.jaut.2015.04.003. Epub 2015 May 4.
Anti-glomerular basement membrane (GBM) disease is a rare autoantibody-mediated disorder presenting as rapidly progressive glomerulonephritis, and often with pulmonary hemorrhage. Antibody removal with plasmapheresis and immunosuppressive drugs are the cornerstones of the treatment. Data regarding the use of specific B-cell depleting therapy such as rituximab are lacking.
We conducted a retrospective observational study of 8 patients with severe and/or refractory GBM disease that received rituximab therapy.
Eight patients (2 men, 6 women) with a mean age of 26 ± 13.1 years old were included. Seven had severe renal involvement [median creatinin level was 282 μmol/l, range (65-423)] requiring high immunosuppressive or plasmapheresis dependent, and two had relapse of pulmonary hemorrhage including one with renal failure. Patients received an initial immunosuppressive treatment including steroid and cyclosphosphamide (n = 8) and plasmapheresis (n = 5). Except one late relapse, rituximab therapy was started within two months after diagnosis. All patients except one received 4 weekly dose of rituximab (375 mg(2)). Anti-GBM antibodies were still present in 6/8 patients, at rituximab initiation. Complete remission was observed in 7 out of 8 patients, mostly 3 months after rituximab therapy. After a mean follow-up of 25.6 months (range 4-93), patient and renal survival were 100% and 75% respectively, but rituximab use did not improve GFR. Anti-GBM antibodies remained negative for all patients during follow-up. Only one patient developed a severe bacterial infection but no opportunistic or viral infections were reported.
Rituximab may represent an additional and/or alternative therapy in the induction treatment of anti-GBM disease.
抗肾小球基底膜 (GBM) 病是一种罕见的自身抗体介导的疾病，表现为快速进行性肾小球肾炎，常伴有肺出血。使用血浆置换和免疫抑制药物清除抗体是治疗的基石。关于利妥昔单抗等特定 B 细胞耗竭疗法的使用数据尚缺乏。
我们对 8 例接受利妥昔单抗治疗的严重和/或难治性 GBM 疾病患者进行了回顾性观察研究。
8 例患者（2 例男性，6 例女性），平均年龄 26±13.1 岁。7 例有严重的肾脏受累[中位数肌酐水平为 282μmol/L，范围（65-423）]，需要高剂量免疫抑制剂或依赖血浆置换，2 例有肺出血复发，其中 1 例合并肾功能衰竭。患者接受了初始免疫抑制治疗，包括类固醇和环磷酰胺（n=8）和血浆置换（n=5）。除 1 例晚期复发外，利妥昔单抗治疗均在诊断后 2 个月内开始。除 1 例外，所有患者均接受了 4 个每周剂量的利妥昔单抗（375mg(2)）。在利妥昔单抗起始时，6/8 例患者的抗 GBM 抗体仍存在。7/8 例患者观察到完全缓解，大多在利妥昔单抗治疗后 3 个月。在平均 25.6 个月（4-93 个月）的随访后，患者和肾脏存活率分别为 100%和 75%，但利妥昔单抗的使用并未改善 GFR。所有患者在随访期间抗 GBM 抗体均为阴性。仅 1 例患者发生严重细菌感染，但未报告机会性或病毒性感染。
利妥昔单抗可能是抗 GBM 病诱导治疗的另一种选择。
