Endophilin A2 Deficiency Impairs Antibody Production in Humans.

Publisher: Springer Country of Publication: Netherlands NLM ID: 8102137 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-2592 (Electronic) Linking ISSN: 02719142 NLM ISO Abbreviation: J Clin Immunol Subsets: MEDLINE

Publication: Amsterdam : Springer
Original Publication: New York : Plenum, c1981-

B-Lymphocytes*/immunology ; Antibody Formation*/genetics ; Antibody Formation*/immunology; Humans ; Male ; Adolescent ; Exome Sequencing ; Pedigree ; Acyltransferases/genetics ; Frameshift Mutation ; Immunoglobulin G/blood ; Immunoglobulin G/immunology

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.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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Keywords: Endophilin A2; Exome sequencing; Predominantly antibody deficiency; SH3GL1

EC 2.3.- (Acyltransferases)
EC 2.3.1.52 (2-acylglycerophosphate acyltransferase)
0 (Immunoglobulin G)

Date Created: 20241105 Date Completed: 20241105 Latest Revision: 20241205

20241209

10.1007/s10875-024-01827-1

39499372