IKBKG (nuclear factor-kappa B essential modulator) mutation can be associated with opportunistic infection without impairing Toll-like receptor function.
J Allergy Clin Immunol
; 121(4): 976-82, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18179816
ABSTRACT
BACKGROUND:
Patients with hypomorphic nuclear factor-kappaB essential modulator (NEMO) mutations have extensive phenotypic variability that can include atypical infectious susceptibility.OBJECTIVE:
This study may provide important insight into immunologic mechanisms of host defense.METHODS:
Immunologic evaluation, including studies of Toll-like receptor (TLR) function, was performed in a 6-month-old boy with normal ectodermal development who was diagnosed with Pneumocystis pneumonia and cytomegalovirus sepsis.RESULTS:
Genomic and cDNA sequencing demonstrated a novel NEMO missense mutation, 337G->A, predicted to cause a D113N (aspartic acid to asparagine) substitution in the first coiled-coil region of the NEMO protein. Quantitative serum immunoglobulins, lymphocyte subset numbers, and mitogen-induced lymphocyte proliferation were essentially normal. The PBMC responses to TLR ligands were also surprisingly normal, whereas natural killer cell cytolytic activity, T-cell proliferative responses to specific antigens, and T-cell receptor-induced NF-kappaB activation were diminished.CONCLUSION:
Unlike the unique NEMO mutation described here, the most commonly reported mutations are clustered at the 3' end in the tenth exon, which encodes a zinc finger domain. Because specific hypomorphic variants of NEMO are associated with distinctive phenotypes, this particular NEMO mutation highlights a dispensability of the region including amino acid 113 for TLR signaling and ectodysplasin A receptor function. This region is required for certain immunoreceptor functions as demonstrated by his susceptibility to infections as well as natural killer cell and T-cell defects.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia por Pneumocystis
/
Infecções Oportunistas
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Pneumocystis carinii
/
Quinase I-kappa B
/
Receptores Toll-Like
/
Mutação
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
/
Infant
/
Male
Idioma:
En
Revista:
J Allergy Clin Immunol
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos