A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency.

ABSTRACT: Interferon regulatory factor 4 (IRF4) is a transcription factor (TF) and key regulator of immune cell development and function. We report a recurrent heterozygous mutation in IRF4, p.T95R, causing an autosomal dominant combined immunodeficiency (CID) in seven patients from six unrelated families. The patients exhibited profound susceptibility to opportunistic infections, notably Pneumocystis jirovecii, and presented with agammaglobulinemia. Patients' B cells showed impaired maturation, decreased immunoglobulin isotype switching, and defective plasma cell differentiation, whereas their T cells contained reduced T_H17 and T_FH populations and exhibited decreased cytokine production. A knock-in mouse model of heterozygous T95R showed a severe defect in antibody prod

SUBMITTER: IRF4 International Consortium 

PROVIDER: S-EPMC10825898 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature