Hyper-IgE syndrome is not associated with defects in several candidate toll-like receptor pathway genes.
Hum Immunol
; 66(7): 842-7, 2005 Jul.
Article
em En
| MEDLINE
| ID: mdl-16112032
ABSTRACT
The genetic basis of hyper-IgE syndrome (HIES), also known as Job syndrome, a primary immunodeficiency associated with recurrent skin and pulmonary infections, is unknown. We hypothesized that HIES is due to a defect in the Toll-like receptor signaling pathway. We used a whole blood cytokine assay to compare inflammatory responses to stimulation with specific Toll-like receptor (TLR) pathway agonists in four individuals with HIES and nine healthy controls. Production of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-12 was not impaired in response to stimulation with lipopolysaccharide, peptidoglycan, zymosan, lipoteichoic acid, Staphylococcus aureus, Escherichia coli, or Streptococcus pneumoniae. Interferon (IFN)-gamma was reduced in HIES subjects in response to each of these stimuli. We sequenced several candidate genes from the TLR pathway in HIES individuals to determine whether any mutations were associated with this syndrome. No novel mutations or polymorphisms were found in the coding regions of TLR1, TLR2, TLR6, MyD88, or TRAF6. In summary, although HIES individuals had an IFN-gamma secretion defect, they also produced normal levels of several TLR-regulated proinflammatory cytokines. No unique mutations or polymorphisms were observed in several candidate genes from the TLR pathway. Our studies do not support a role for a defective TLR response in HIES individuals.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Receptores Toll-Like
/
Síndrome de Job
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Hum Immunol
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos