Quantitative defects in invariant NKT cells and TLR responses in patients with hyper-IgE syndrome.

Abstract:

BACKGROUND:Autosomal dominant hyper-IgE syndrome (AD-HIES) is a primary immunodeficiency mainly caused by mutations in STAT3, a signalling molecule implicated in the development of appropriate immune responses. We aimed to characterise the innate immune response in AD-HIES. METHODS:The frequency of innate immune cells in peripheral blood (PB) from seven AD-HIES patients and healthy controls were determined. CD80/CD86 surface expression and cytokine levels in supernatants from PBMC after stimulation with TLR-2, -4 and -9 agonists were also measured by flow cytometry. In addition, several SNPs within these TLR genes in genomic DNA samples from patients and controls were examined. RESULTS:A significantly reduced number of PB iNKT cells was observed in the AD-HIES group. CpG-stimulated pDC and mDC from patients exhibited a lower increase in the expression of the costimulatory molecule CD80. We also observed an increase in the secretion of IL-12p70, TNF-alpha and IL-10 in PBMC from HIES patients after LTA or LPS stimuli. No association was found between the different SNPs detected and the HIES phenotype. CONCLUSIONS:These findings demonstrate that important mediators of the innate immunity responses are affected in AD-HIES. More studies are necessary to investigate how the STAT3 function interferes with development of iNKT cells and TLR-mediated responses.

authors

Gutierrez-Hincapié S,Muskus-López CE,Montoya CJ,Trujillo-Vargas CM

doi

10.1016/j.aller.2014.11.002

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

553-61

issue

6

eissn

0301-0546

issn

1578-1267

pii

S0301-0546(15)00023-3

journal_volume

43

pub_type

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