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Mold-sensitivity in children with moderate-severe asthma is associated with HLA-DR and HLA-DQ.

Abstract：

BACKGROUND:Several epidemiologic studies in the United States and Europe have linked Alternaria sensitivity to both persistence and severity of asthma. In this study, we examined T cell responses and HLA class II alleles in children with moderate-severe asthma. METHODS:Ninety-six children with moderate-severe asthma were compared to 90 children with mild asthma. HLA class II genotyping was performed to determine HLA allelic frequencies. Th1/Th2 Alternaria-specific T cell cytokine responses were determined by the use of Alternaria-stimulated cultures. HLA class II restriction was examined by inhibition of Alternaria-stimulated lymphoproliferative responses with blocking anti-HLA class II monoclonal antibodies. RESULTS:Children with moderate-severe asthma had significantly increased sensitivities to Aspergillus fumigatus; sensitivities to Alternaria were similar in both moderate-severe and mild asthmatics. The frequency of HLA-DRB1*13 alleles were increased in mold-sensitive moderate-severe asthmatic children. HLA-DRB1*03 tended to be increased in mold-sensitive moderate-severe asthmatics. The frequency of HLA-DQB1*03 alleles was significantly decreased in mold and Alternaria-sensitive moderate-severe asthma. HLA class II blocking monoclonal antibodies demonstrated HLA-DR restriction. Alternaria-stimulated IL-5 and IL-13 synthesis was significantly increased in moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in Alternaria-stimulated lymphocyte cultures of HLA-DQB1*03- asthmatics compared to HLA-DQB1*03+ asthmatics. CONCLUSIONS:In children with Alternaria-sensitive moderate-severe asthma, there was increased Th2 sensitivity to Alternaria stimulation. This was associated with HLA-DR restriction and with increased frequency of HLA-DRB1*13 and HLA-DRB1*03. There was decreased frequency of HLA-DQB1*03 in Alternaria-sensitive moderate-severe asthma, suggesting HLA-DQB1*03 may be protective of the development of Alternaria-sensitive severe asthma.

journal_name

Allergy

journal_title

Allergy

authors

Knutsen AP,Vijay HM,Kumar V,Kariuki B,Santiago LA,Graff R,Wofford JD,Shah MR

doi

10.1111/j.1398-9995.2010.02382.x

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

1367-75

issue

eissn

0105-4538

issn

1398-9995

pii

ALL2382

journal_volume

pub_type

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Mold-sensitivity in children with moderate-severe asthma is associated with HLA-DR and HLA-DQ.