Endophilin A2 Deficiency Impairs Antibody Production in Humans.

IF 7.2 2区 医学 Q1 IMMUNOLOGY Journal of Clinical Immunology Pub Date : 2024-11-05 DOI:10.1007/s10875-024-01827-1
Cybel Mehawej, Eliane Chouery, Roula Farah, Alia Khalil, Setrida El Hachem, Sandra Corbani, Valerie Delague, Issam Mansour, Tarek Najemdeen, Rima Korban, Wissam H Faour, Gerard Lefranc, Andre Megarbane
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Abstract

Endophilin A2, the sole endophilin A family member expressed in hematopoietic cells, regulates various aspects of membrane dynamics, including autophagy and endocytosis. Recent studies in rodents highlight the essential role of endophilin A2 in modulating immune responses. Here we report a homozygous frameshift variant in the SH3GL1 gene (NM_003025.3:c.427delC; p.Leu143Serfs*9), detected by whole exome sequencing in a 14-year-old boy with predominantly antibody deficiency. The patient who is issued from a consanguineous Lebanese family, presents since the age of 18 months with recurrent respiratory tract infections, low peripheral B cell counts and pan-hypogammaglobulinemia, with no history of opportunistic infections. This defect is associated with decrease in switched memory B cells development, impaired in-vitro B cell proliferation and diminished in-vitro IgG production. The detected variant in SH3GL1 segregates with the disease in the family. It significantly decreases the expression of the protein in the patient's peripheral blood compared to healthy controls, thus confirming its pathogenicity. Interestingly, endophilin A2-deficient Sh3gl1-/- mice have been reported to present defects in germinal center B cell responses and in the production of high-affinity IgG. Our data suggests that endophilin A2 deficiency impairs antibody production in humans. Reporting further cases with mutations in SH3GL1 is needed to better characterize the inborn error of immunity linked to this gene.

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嗜内酯蛋白 A2 缺乏会影响人体抗体的产生
嗜内酯蛋白 A2 是造血细胞中唯一表达的嗜内酯蛋白 A 家族成员,它调节膜动力学的各个方面,包括自噬和内吞。最近在啮齿类动物中进行的研究强调了嗜内蛋白 A2 在调节免疫反应中的重要作用。在此,我们报告了通过全外显子组测序在一名主要患有抗体缺乏症的 14 岁男孩体内检测到的 SH3GL1 基因(NM_003025.3:c.427delC; p.Leu143Serfs*9)同位框移变异。患者来自一个近亲结婚的黎巴嫩家庭,从 18 个月大开始就出现反复呼吸道感染、外周 B 细胞计数低和泛高丙种球蛋白血症,但没有机会性感染病史。这种缺陷与开关记忆 B 细胞发育下降、体外 B 细胞增殖受损和体外 IgG 生成减少有关。检测到的 SH3GL1 变异与该家族的疾病有分离关系。与健康对照组相比,患者外周血中该蛋白的表达明显减少,从而证实了其致病性。有趣的是,有报道称嗜内蛋白 A2 缺失的 Sh3gl1-/- 小鼠在生殖中心 B 细胞反应和高亲和性 IgG 的产生方面存在缺陷。我们的数据表明,嗜内脂素 A2 缺乏会损害人类的抗体生成。需要进一步报告 SH3GL1 基因突变的病例,以更好地描述与该基因相关的先天性免疫错误。
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来源期刊
CiteScore
12.20
自引率
9.90%
发文量
218
审稿时长
2 months
期刊介绍: The Journal of Clinical Immunology publishes impactful papers in the realm of human immunology, delving into the diagnosis, pathogenesis, prognosis, or treatment of human diseases. The journal places particular emphasis on primary immunodeficiencies and related diseases, encompassing inborn errors of immunity in a broad sense, their underlying genotypes, and diverse phenotypes. These phenotypes include infection, malignancy, allergy, auto-inflammation, and autoimmunity. We welcome a broad spectrum of studies in this domain, spanning genetic discovery, clinical description, immunologic assessment, diagnostic approaches, prognosis evaluation, and treatment interventions. Case reports are considered if they are genuinely original and accompanied by a concise review of the relevant medical literature, illustrating how the novel case study advances the field. The instructions to authors provide detailed guidance on the four categories of papers accepted by the journal.
期刊最新文献
A large cohort from an immunology reference center and an algorithm for the follow-up of chronic neutropenia. Endophilin A2 Deficiency Impairs Antibody Production in Humans. Polysaccharide, Conjugate, and mRNA-based Vaccines are Immunogenic in Patients with Netherton Syndrome. Hematopoietic Stem Cell Transplantation for C1q Deficiency: A Study on Behalf of the EBMT Inborn Errors Working Party. Cancer Trends in Inborn Errors of Immunity: A Systematic Review and Meta-Analysis.
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