AIOLOS Variants Causing Immunodeficiency in Human and Mice

• Published in: Frontiers in immunology Vol. 13; p. 866582
• Main Authors: Yamashita, Motoi, Morio, Tomohiro
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 04.04.2022
• Subjects: AIOLOS; Animals; B-Lymphocytes; Epstein-Barr Virus Infections - pathology; Herpesvirus 4, Human - metabolism; Humans; IKAROS; Ikaros Transcription Factor - genetics; Ikaros Transcription Factor - metabolism; IKZF transcription factor; IKZF3; Immunologic Deficiency Syndromes - metabolism; Immunology; inborn errors of immunity; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Mice; IKZF transcription factor; inborn errors of immunity; AIOLOS; IKZF3; IKAROS
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.866582

AIOLOS is encoded by IKZF3 and is a member of the IKAROS zinc finger transcription factor family. Heterozygous missense variants in the second zinc finger of AIOLOS have recently been reported to be found in the families of patients with inborn errors of immunity. The AIOLOS G159R variant was identified in patients with B-lymphopenia and familial Epstein–Barr virus-associated lymphoma. Early B-cell progenitors were significantly reduced in the bone marrow of patients with AIOLOS G159R . Another variant, AIOLOS N160S was identified in the patients presented with hypogammaglobulinemia, susceptibility to Pneumocystis jirovecii pneumonia, and chronic lymphocytic leukemia. Patients with AIOLOS N160S had mostly normal B cell counts but showed increased levels of CD21 lo B cells, decreased CD23 expression, and abrogated CD40 response. Both variants were determined to be loss-of-function. Mouse models harboring the corresponding patient’s variants recapitulated the phenotypes of the patients. AIOLOS is therefore a novel disease-causing gene in human adaptive immune deficiency.