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- Title
Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations.
- Authors
Orange, Jordan S; Brodeur, Scott R; Jain, Ashish; Bonilla, Francisco A; Schneider, Lynda C; Kretschmer, Roberto; Nurko, Samuel; Rasmussen, Wendy L; Köhler, Julia R; Gellis, Stephen E; Ferguson, Betsy M; Strominger, Jack L; Zonana, Jonathan; Ramesh, Narayanaswamy; Ballas, Zuhair K; Geha, Raif S
- 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.
- Publication
The Journal of clinical investigation, 2002, Vol 109, Issue 11, p1501
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI14858