More Severe Than Cvid: Combined Immunodeficiency Due To A Novel Nfkb2 Mutation

The nuclear factor kappa-B (NF-κB) signaling pathway is crucial in inflammatory and immune responses. NF-κB2 plays a pivotal role in the noncanonical pathway important for peripheral lymphoid organ development, B-cell maturation and antibody production. 1 Heterozygous mutations in the NFKB2 gene have been identified as a molecular cause of primary immunodeficiency. Previously described NF-κB2-defective patients presented with hypogammaglobulinemia in early childhood and suffered from recurrent respiratory tract infections. 2 Clinical and immunological features are often compatible with common variable immunodeficiency (CVID), but additional defects in T and NK cells have been reported. 3-5,9 . Other typical symptoms such as ectodermal dysplasia with alopecia totalis and trachyonychia may be autoimmune manifestations. About half of the patients develop isolated ACTH deficiency with consecutive cortisol deficiency, an unusual feature in large cohorts of CVID patients. Susceptibility to herpes infections has also been described.