biostudies-literatureUnknown218(12)Kuehn HSRIKEN Center for Integrative Medical SciencesNIH Clinical CenterNational Institutes of HealthNIH HHSAIOLOS/IKZF3 is a member of the IKAROS family of transcription factors. IKAROS/IKZF1 mutations have been previously associated with different forms of primary immunodeficiency. Here we describe a novel combined immunodeficiency due to an IKZF3 mutation in a family presenting with T and B cell involvement, Pneumocystis jirovecii pneumonia, and/or chronic lymphocytic leukemia. Patients carrying the AIOLOS p.N160S heterozygous variant displayed impaired humoral responses, abnormal B cell development (high percentage of CD21low B cells and negative CD23 expression), and abrogated CD40 responses. Naive T cells were increased, T cell differentiation was abnormal, and CD40L expression was dysregulated. In vitro studies demonstrated that the mutant protein failed DNA binding and pericentromeric taThe Journal of experimental medicinee20211118https://www.ebi.ac.uk/biostudies/studies/S-EPMC8548914biostudies-literatureT and B cell abnormalities, pneumocystis pneumonia, and chronic lymphocytic leukemia associated with an AIOLOS defect in patients.PMC8548914Taniuchi INiemela JEStoddard JLNunes-Santos CJBoast BFleisher TAZou CBaxter RMMorio TRosenzweig SDHarada JOkuyama KKuehn HSChang JGarofalo MDutmer CMYamashita MHsieh EWYfalseT and B cell abnormalities, pneumocystis pneumonia, and chronic lymphocytic leukemia associated with an AIOLOS defect in patients.AIOLOS/IKZF3 is a member of the IKAROS family of transcription factors. IKAROS/IKZF1 mutations have been previously associated with different forms of primary immunodeficiency. Here we describe a novel combined immunodeficiency due to an IKZF3 mutation in a family presenting with T and B cell involvement, Pneumocystis jirovecii pneumonia, and/or chronic lymphocytic leukemia. Patients carrying the AIOLOS p.N160S heterozygous variant displayed impaired humoral responses, abnormal B cell development (high percentage of CD21low B cells and negative CD23 expression), and abrogated CD40 responses. Naive T cells were increased, T cell differentiation was abnormal, and CD40L expression was dysregulated. In vitro studies demonstrated that the mutant protein failed DNA binding and pericentromeric ta2021-01-01T00:00:00Z2021 Dec2026-05-08T18:28:55.966Z2022-02-11T13:29:16.21ZS-EPMC85489143469436610.1084/jem.20211118