From the Clinical Immunology and Primary Immunodeficiencies Unit (A.D.-M., A.E.-S., A.G.-G., L.A.), Pediatric Allergy and Clinical Immunology Department (A.D.-M., Y.G., M.P., A.E.-S., A.G.-G., A.M.P., L.A.), Hospital Sant Joan de Déu, Barcelona, Spain; Institut de Recerca Sant Joan de Déu (A.D.-M., Y.G., M.P., A.E.-S., J.A., A.G.-G., A.M.P., L.A.), Barcelona, Spain; Clinical Immunology Unit Hospital Sant Joan de Déu-Hospital Clínic (A.D.-M., A.V., M.P., M.J., A.E.-S., A.G.-G., A.M.P., L.A.), Barcelona, Spain; Universitat de Barcelona (J.A., L.A., M.J.), Spain; Immunology Department (A.V., M.J.), Biomedical Diagnostics Center, Hospital Clinic-IDIBAPS, Barcelona, Spain; Pediatric Neuroimmunology Unit (C.M.-A., T.A.), Neurology Department, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain; Neuroimmunology Program (T.A.), Institut D'Investigacions Biomèdiques (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain; Pediatric Rheumatology Division (J.A.), Hospital Sant Joan de Déu, Barcelona, Spain; and Pediatric Nephrology Department (Á.M.), Hospital Sant Joan de Déu, Barcelona, Spain.
Neurol Neuroimmunol Neuroinflamm. 2020 May 6;7(4). doi: 10.1212/NXI.0000000000000724. Print 2020 Jul.
To investigate the immunologic impact of a single cycle of rituximab (RTX) in children and adolescents with immune-mediated disorders, we evaluated B cells and immunoglobulin levels of 20 patients with neuroimmunologic, nephrologic, dermatologic, and rheumatologic disorders treated under recommended guidelines.
Retrospective study of immunologic changes in children (aged ≤18 years) diagnosed with immune-mediated disorders in which RTX was prescribed between June 2014 and February 2019. Patients were excluded if they had prior diagnosis of malignant disease or primary immunodeficiency. Patients were clinically and immunologically followed up every 3 months. Only patients having received a single cycle of RTX and with a follow-up greater than 12 months were included in the analysis of persistent dysgammaglobulinemia.
Twenty children were included. Median age at RTX treatment was 12.8 years (interquartile range [IQR] 6.6-15.5 years). Median follow-up was 12.6 months (IQR 10.2-24 months). Of the 14 patients eligible for persistent dysgammaglobulinemia analysis (3 had received RTX retreatment, 2 had <12 months post-RTX follow-up, and in 1 data for this time point was missing), 2/14 (14%) remained with complete B-cell depletion, and 5/14 (36%) had dysgammaglobulinemia. Patients with dysgammaglobulinemia were younger (7.8 vs 15.6 years, = 0.072), had more underlying neuroimmunologic diseases (5/5 vs 0/9, < 0.001), and had received more frequently concentrated doses of RTX (3/5 vs 1/9, = 0.05) than patients without dysgammaglobulinemia. Kinetics of immunoglobulins in the 20 patients revealed a decrease as early as 3 months after RTX in patients with neuroimmunologic disorders.
In our cohort, single-cycle RTX-induced dysgammaglobulinemia was enhanced in patients with neuroimmunologic diseases. Further studies are needed to confirm this observation.
为了研究单次利妥昔单抗（RTX）治疗对儿童和青少年免疫介导性疾病的免疫影响，我们评估了 20 例接受推荐指南治疗的神经免疫、肾脏、皮肤和风湿性疾病患者的 B 细胞和免疫球蛋白水平。
对 2014 年 6 月至 2019 年 2 月期间因免疫介导性疾病而接受 RTX 治疗的儿童（≤18 岁）的免疫变化进行回顾性研究。排除患有恶性肿瘤或原发性免疫缺陷的患者。对患者进行临床和免疫随访，每 3 个月一次。仅纳入接受过单次 RTX 治疗且随访时间超过 12 个月的患者进行持续性低丙种球蛋白血症分析。
共纳入 20 例患儿。RTX 治疗时的中位年龄为 12.8 岁（四分位距[IQR]6.6-15.5 岁）。中位随访时间为 12.6 个月（IQR 10.2-24 个月）。在 14 例适合持续性低丙种球蛋白血症分析的患者中（3 例接受了 RTX 再治疗，2 例在 RTX 后随访时间<12 个月，1 例在此时间点的数据缺失），2/14（14%）例患者仍存在完全 B 细胞耗竭，5/14（36%）例患者存在低丙种球蛋白血症。低丙种球蛋白血症患者更年轻（7.8 岁比 15.6 岁， = 0.072），更常患有神经免疫性疾病（5/5 例比 0/9 例， < 0.001），且更常接受集中剂量的 RTX（3/5 例比 1/9 例， = 0.05）。20 例患者的免疫球蛋白动力学显示，神经免疫性疾病患者在 RTX 后 3 个月即出现免疫球蛋白下降。
在我们的队列中，单次 RTX 诱导的低丙种球蛋白血症在神经免疫性疾病患者中更为明显。需要进一步的研究来证实这一观察结果。
