Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations.
Article Details
- CitationCopy to clipboard
Orange JS, Brodeur SR, Jain A, Bonilla FA, Schneider LC, Kretschmer R, Nurko S, Rasmussen WL, Kohler JR, Gellis SE, Ferguson BM, Strominger JL, Zonana J, Ramesh N, Ballas ZK, Geha RS
Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations.
J Clin Invest. 2002 Jun;109(11):1501-9.
- PubMed ID
- 12045264 [ View in PubMed]
- Abstract
NF-kappaB essential modifier (NEMO), also known as IKK-gamma, is a member of the I-kappaB kinase complex responsible for phosphorylating I-kappaB, allowing the release and activation of NF-kappaB. Boys with an expressed NEMO mutation have an X-linked syndrome characterized by hypohidrotic ectodermal dysplasia with immune deficiency (HED-ID). The immunophenotype resulting from NEMO mutation is highly variable, with deficits in both T and B cell responses. We evaluated three patients with NEMO mutations (L153R, Q403X, and C417R) and HED-ID who had evidence of defective CD40 signaling. All three patients had normal percentages of peripheral blood NK cells, but impaired NK cell cytotoxic activity. This was not due to a generalized defect in cytotoxicity because antibody-dependent cellular cytotoxicity was intact. This abnormality was partially reversed by in vitro addition of IL-2, which was also able to induce NF-kappaB activation. In one patient with recurrent cytomegalovirus infections, administration of IL-2 partially corrected the NK cell killing deficit. These data suggest that NEMO participates in signaling pathways leading to NK cell cytotoxicity and that IL-2 can activate NF-kappaB and partially overcome the NK cell defect in patients with NEMO mutations.