Department of Clinical Immunology, National Children Medical Center, Children's Hospital of Fudan University, Shanghai, 201102, China.
Ministry of Education Key Laboratory of Contemporary Anthropology, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, 200438, China.
J Clin Immunol. 2024 Apr 18;44(4):102. doi: 10.1007/s10875-024-01705-w.
Autoimmunity is a significant feature of APDS1 patients. We aimed to explore the pathogenic immune phenotype and possible mechanisms of autoimmunity in APDS1 patients.
The clinical records and laboratory data of 42 APDS1 patients were reviewed. Immunophenotypes were evaluated by multiparametric flow cytometry. Autoantibodies were detected via antigen microarray analysis.
A total of 42 children with PIK3CD gene mutations were enrolled. Immunological tests revealed increased proportions of effector memory cells (86%) and central memory cells (59%) among CD4+ T cells; increased proportions of effector memory cells (83%) and terminally differentiated effector memory T cells (38%) among CD8+ T cells. Fewer CD3+ T cells and B cells and higher IgG levels were reported in patients with autoimmunity. The proportion of Tregs was decreased, and the proportions of Th9, Tfh, and Tfr cells were increased in APDS1 patients. Among APDS1 patients, higher proportion of Th2 and Tfr cells were found in those with autoimmunity. The proportions of CD11c+ B and CD21lo B cells in patients with autoimmunity were significantly increased. Antigen microarray analysis revealed a wide range of IgG/IgM autoantibodies in patients with APDS1. In patients with autoimmunity, the proportion of Tfr might be positively correlated with autoantibodies.
The pathogenic immune phenotype of APDS1 patients included (1) deceased CD3+ T-cell and B-cell counts and increased IgG levels in patients with autoimmunity, (2) an imbalanced T helper cell subset, (3) increased proportions of autoreactive B cells, and (4) distinct autoantibody reactivities in patients with autoimmunity.
自身免疫是 APDS1 患者的一个显著特征。本研究旨在探索 APDS1 患者发生自身免疫的致病免疫表型及可能机制。
回顾性分析 42 例 APDS1 患者的临床资料和实验室数据。采用多参数流式细胞术评估免疫表型，通过抗原微阵列分析检测自身抗体。
共纳入 42 例 PIK3CD 基因突变患儿。免疫检测显示，APDS1 患者 CD4+T 细胞中效应记忆细胞（86%）和中央记忆细胞（59%）比例升高，CD8+T 细胞中效应记忆细胞（83%）和终末分化效应记忆 T 细胞（38%）比例升高。自身免疫组患者 CD3+T 细胞和 B 细胞减少，IgG 水平升高。Treg 比例降低，Th9、Tfh 和 Tfr 细胞比例升高。APDS1 患者中，自身免疫组 Th2 和 Tfr 细胞比例较高。自身免疫组患者 CD11c+B 和 CD21loB 细胞比例明显升高。抗原微阵列分析显示，APDS1 患者 IgG/IgM 自身抗体谱广泛。自身免疫组患者 Tfr 比例与自身抗体呈正相关。
APDS1 患者的致病免疫表型包括（1）自身免疫患者 CD3+T 细胞和 B 细胞计数减少，IgG 水平升高；（2）辅助性 T 细胞亚群失衡；（3）自身反应性 B 细胞比例增加；（4）自身免疫患者存在独特的自身抗体反应。
