Division of Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Scand J Immunol. 2019 Jun;89(6):e12759. doi: 10.1111/sji.12759. Epub 2019 Mar 18.
DOCK8 immunodeficiency syndrome (DIDS) is a combined immunodeficiency characterized by recurrent viral infections, severe atopy and early onset malignancy. Immunological abnormalities include lymphopenia, CD8 T-cell cytoskeleton dysfunction, defective B cell memory and variable serum immunoglobulin levels. Here, we analyse the B cell receptor repertoire (BCR) characteristics and antibody avidity of four DIDS patients, attempt to understand the dysregulated humoral immunity in DIDS patients with a normal antibody titre and suggest a scientific basis for intravenous immunoglobulin (IVIG) replacement therapy for these patients. We analysed BCR characteristics, including somatic hypermutation (SHM) frequency, using deep sequencing of multiplex PCR products derived from BCR heavy chain CDR3 regions from DIDS patients and controls. The antibody avidity of human tetanus and hemophilus influenza B antibodies was determined by ELISA using thiocyanate elution. IVIG replacement treatment and infection conditions were investigated retrospectively. We found skewing of the BCR repertoire and decreased antibody avidity in patients with DIDS. DIDS patients had fewer negatively charged amino acids than healthy controls. The SHM frequency of the IGHV3 gene was lower in patients with DIDS. Patients received regular IVIG therapy, resulting in fewer and less severe infections. We conclude that although IgG levels are normal in most DIDS patients, IVIG replacement therapy is still necessary.
DOCK8 免疫缺陷综合征（DIDS）是一种联合免疫缺陷症，其特征为反复发生的病毒感染、严重的特应性皮炎和早期恶性肿瘤。免疫异常包括淋巴细胞减少症、CD8 T 细胞细胞骨架功能障碍、B 细胞记忆缺陷和血清免疫球蛋白水平变化。在这里，我们分析了四名 DIDS 患者的 B 细胞受体（BCR）特征和抗体亲和力，试图了解 DIDS 患者中具有正常抗体滴度的失调性体液免疫，并为这些患者的静脉注射免疫球蛋白（IVIG）替代疗法提供科学依据。我们分析了 BCR 特征，包括体细胞高频突变（SHM）频率，使用多重 PCR 产物的深度测序，从 DIDS 患者和对照的 BCR 重链 CDR3 区域获得。使用硫氰酸盐洗脱通过 ELISA 测定人破伤风和流感嗜血杆菌 B 型抗体的抗体亲和力。回顾性研究了 IVIG 替代治疗和感染情况。我们发现 DIDS 患者的 BCR 谱偏向和抗体亲和力降低。DIDS 患者的负电荷氨基酸比健康对照组少。IGHV3 基因的 SHM 频率在 DIDS 患者中较低。患者接受了常规 IVIG 治疗，感染次数减少且程度较轻。我们得出结论，尽管大多数 DIDS 患者的 IgG 水平正常，但仍需要 IVIG 替代治疗。
