Mold-sensitivity in Children With Moderate-Severe Asthma Is Associated With HLA-DR and HLA-DQ

Allergy. 2010 Nov;65(11):1367-75. doi: 10.1111/j.1398-9995.2010.02382.x. Epub 2010 Jun 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asthma / etiology
  • Asthma / genetics*
  • Asthma / immunology
  • Child
  • Child, Preschool
  • Cytokines / biosynthesis
  • Female
  • Fungi / immunology*
  • Genetic Predisposition to Disease / genetics*
  • HLA-DQ Antigens / genetics*
  • HLA-DQ Antigens / immunology
  • HLA-DR Antigens / genetics*
  • HLA-DR Antigens / immunology
  • Humans
  • Hypersensitivity / genetics*
  • Hypersensitivity / immunology
  • Male

Substances

  • Cytokines
  • HLA-DQ Antigens
  • HLA-DR Antigens