[Incidence of hypogammaglobulinaemia in children with steroid-dependent/frequently relapsing nephrotic syndrome treated with rituximab and its association with severe infections].

Objective: To investigate the incidence and influencing factors of hypogammaglobulinemia (HGG) in children with steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) treated with rituximab (RTX), and its relationship with the risk of severe infections. Methods: The clinical data of children with SDNS/FRNS treated with RTX at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University from December 2020 to January 2023 were retrospectively analyzed. RTX treatment was performed using a B-cell-guided regimen (a single dose of 375 mg/m2, a maximum of 500 mg/dose, and an additional one dose when reassessment of peripheral blood CD19+B cells≥1%). Patients were divided into HGG and non-HGG groups according to the presence or absence of HGG during the follow-up period. A multivariate logistic regression model was used to analyze the influencing factors of HGG, and the predictive value of each influencing factor on HGG was assessed by plotting the receiver operating characteristic (ROC) curve. Results: A total of 59 SDNS/FRNS children (48 males and 11 females) were included, and aged [M (Q1, Q3)] 9.4 (6.5, 12.2) years at the time of the first RTX treatment, with a median application of 3 (2, 4) doses of RTX. During the follow-up period of 15.5 (9.9, 22.8) months, the HGG was present in 16 (27.1%) children, of which seven persisted for more than 1 year. Compared with non-HGG group, HGG group had a shorter duration of the disease [3.3 (2.1, 3.6) vs 4.6 (2.4, 8.0) years, P=0.030], younger age at the time of the first RTX treatment [6.2 (5.6, 7.4) vs 11.3 (8.8, 13.3) years, P<0.001], and lower serum IgG levels [5.9 (4.9, 6.4) vs 7.5 (6.1, 8.2) g/L, P<0.001]. Multivariate logistic regression analysis showed that young age at the time of the first RTX treatment (OR=0.52, 95%CI: 0.35-0.78, P=0.002) was an influencing factor of HGG. The area under the curve (AUC) for age at first RTX treatment to predict HGG was 0.887 (95%CI: 0.778-0.955, P<0.001), with an optimal cut-off value of 8.3 years. During the follow-up period, six children (10.2%) developed severe infectious, and there was no statistically significant difference in the incidence of serious infections between the HGG and non-HGG groups [12.5% (2/16) vs 9.3% (4/43), P=1.000]. Conclusions: HGG is frequent in children with SDNS/FRNS treated with RTX, and nearly half of HGG persists for more than 1 year. The possibility of HGG is greater in those≤8.3 years at the first RTX treatment, but HGG does not increase the risk of severe infections in children.目的： 探讨激素依赖/频复发型肾病综合征（SDNS/FRNS）患儿接受利妥昔单抗（RTX）治疗后低丙种球蛋白血症（HGG）的发生率、影响因素及其与严重感染的关系。 方法： 回顾性分析2020年12月至2023年1月于郑州大学第一附属医院儿科接受RTX治疗的SDNS/FRNS患儿的临床资料。RTX治疗采用B细胞指导方案（单次剂量375 mg/m2，最大500 mg/剂，复查外周血CD19+ B细胞≥1%时追加1剂）。根据随访期间是否出现HGG分为HGG组与非HGG组。采用多因素logistic回归模型分析HGG的影响因素，绘制受试者工作特征（ROC）曲线评估各影响因素对HGG的预测价值。 结果： 共纳入59例SDNS/FRNS患儿，男48例，女11例，首次RTX治疗时年龄［M（Q1，Q3）］9.4（6.5，12.2）岁，应用3（2，4）剂RTX。随访15.5（9.9，22.8）个月，16例（27.1%）出现HGG，其中7例持续存在1年以上。与非HGG组相比，HGG组病程较短［3.3（2.1，3.6）比4.6（2.4，8.0）年，P=0.030］，首次RTX治疗时年龄较小［6.2（5.6，7.4）比11.3（8.8，13.3）岁，P<0.001］，血清IgG水平较低［5.9（4.9，6.4）比7.5（6.1，8.2）g/L，P<0.001］。多因素logistic回归分析结果显示，首次RTX治疗时年龄小（OR=0.52，95%CI：0.35~0.78，P=0.002）是HGG的影响因素。首次RTX治疗时年龄预测HGG的AUC为0.887（95%CI：0.778~0.955，P<0.001），最佳截断值为8.3岁。随访期间，6例（10.2%）患儿发生严重感染，HGG组与非HGG组严重感染的发生率差异无统计学意义［12.5%（2/16）比 9.3%（4/43），P=1.000］。 结论： SDNS/FRNS患儿接受RTX治疗后的HGG并不少见，其中近半数HGG持续存在1年以上，首次RTX治疗时年龄≤8.3岁者发生HGG的可能性大，但HGG并未增加患儿的严重感染风险。.