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.

• Authors: A P Knutsen, H M Vijay, V Kumar, B Kariuki, L A Santiago, R Graff, J D Wofford, M R Shah
• Journal: Allergy (Allergy) Vol. 65 Issue 11 Pg. 1367-75 (Nov 2010) ISSN: 1398-9995 [Electronic] Denmark
• PMID: 20486920 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 John Wiley & Sons A/S.

Chemical References

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

Topics

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