Heterozygous NFKB1 variant causes inflammatory dysregulation shaped by broader genetic context in common variable immunodeficiency - PubMed
4 hours ago
- #Immunology
- #Inflammation
- #NF-kappaB
- Heterozygous NFKB1 variants are common in Common Variable Immunodeficiency (CVID) and linked to inflammatory complications.
- CRISPR/Cas9-edited iPSC-derived monocytes (iMONOs) showed that NFKB1 variants reduce NFKB1 protein but increase inflammatory responses only in CVID patient cells.
- CVID patient iMONOs exhibited elevated inflammatory markers like IL-1β, IL-6, TNF, and neutrophil chemoattractants, which were intensified by the NFKB1 variant.
- TNF antagonism improved GI disease in a CVID patient, reducing neutrophilic gastritis and circulating neutrophils.
- The study highlights the role of NFKB1 variants in inflammatory dysregulation in CVID and suggests potential therapeutic targets.