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The following is a summary of “IRF2BP2 Deficiency: An important form of common variable immunodeficiency with inflammation,” published in the March 2025 issue of Journal of Allergy and Clinical Immunology by Udemgba et al. 

Interferon regulatory factor-2 binding protein-2 (IRF2BP2) regulates immune pathways, angiogenesis, apoptosis, and cell differentiation. Its defects lead to immunodeficiency. 

Researchers conducted a retrospective study to characterize and functionally test IRF2BP2 variants in 34 individuals. 

They collected 34 subjects from 18 families with IRF2BP2 mutations. Records were abstracted for clinical phenotypes, and functional testing was performed on peripheral blood mononuclear cells (PBMCs).  Nuclear factor of activated T cells (NFAT) luciferase gene reporter constructs, and quantitative cDNA determinations assessed repressor activity in Jurkat cells with ectopic expression of IRF2BP2 mutant constructs. 

The results showed immunodeficiency in 91% (30/33) with variable gastrointestinal (65%, 20/31) and inflammatory or autoimmune features (57%, 17/30), including chronic abdominal pain, colitis, diarrhea, constipation, vitiligo, alopecia, and migratory rashes. Memory B-cells were reduced with poor immunoglobulin production and lower calcium flux to B-cell receptor stimuli. PBMCs had increased apoptosis in vitro. Patient-derived IRF2BP2 mutants showed impaired NFAT repression and higher TNF-α transcript levels compared to wild-type. 

Investigators found that IRF2BP2 deficiency caused immunodeficiency with gastrointestinal and inflammatory disorders, impaired B-cell maturation, and enhanced proinflammatory signaling through cytokine expression due to impaired NFAT repression. 

Source: jacionline.org/article/S0091-6749(25)00275-1/abstract