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

• Published in: Allergy (Copenhagen) 2010-11, Vol.65 (11), p.1367-1375
• Main Authors: Knutsen, A.P, Vijay, H.M, Kumar, V, Kariuki, B, Santiago, L.A, Graff, R, Wofford, J.D, Shah, M.R
• Format: Article
• Language: English
• Subjects: Adolescent; Alternaria; Alternaria alternata; Aspergillus fumigatus; Asthma; Asthma - etiology; Asthma - genetics; Asthma - immunology; Biological and medical sciences; Child; Child, Preschool; Childrens health; Cytokines - biosynthesis; Dermatology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Fungi - immunology; Genetic Predisposition to Disease - genetics; HLA class II antigens; HLA-DQ Antigens - genetics; HLA-DQ Antigens - immunology; HLA-DR Antigens - genetics; HLA-DR Antigens - immunology; Humans; Hypersensitivity - genetics; Hypersensitivity - immunology; Male; Medical sciences; Mold; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Th2 cytokines
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/j.1398-9995.2010.02382.x

To cite this article: Knutsen AP, Vijay HM, Kumar V, Kariuki B, Santiago LA, Graff R, Wofford JD, Shah MR. Mold-sensitivity in children with moderate-severe asthma is associated with HLA-DR and HLA-DQ. Allergy 2010; 65: 1367-1375. 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. 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. 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. 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.