HLA-DQ3 and Alternaria-sensitive Moderate-severe Asthma In Children
RATIONALE: Sensitivity to Alternaria has been associated with severe asthma. We hypothesized that there may be genetic risks including HLA-DR/DP/DQ associations that may account for this. METHODS: HLA-DR, -DP and -DQ typing was performed on 31 Alternaria-sensitive moderate-severe asthmatic children compared to 37 Alternaria-sensitive mild asthmatic children. Cytokine synthesis was performed on PBMNCs stimulated with Alternaria alternata, Aspergillus fumigatus and Der p extracts. RESULTS: There were no differences of frequencies of HLA-DR and HLA-DP in Alternaria-sensitive moderate-severe asthmatics compared to mild asthmatics. HLA-DQ3 was significantly decreased in moderate-severe asthmatics compared to mild asthmatics, 36% vs 68% (p < 0.01). IL-5 and IL-13 synthesis was significantly increased in Alternaria stimulated cultures of moderate-severe asthmatics (p < 0.05 and <0.02, respectively), but not to Aspergillus and Der p stimulations. In HLA-DQ3- Alternaria-sensitive asthmatics, IL-5 and IL-13 synthesis to Alternaria stimulation was significantly increased compared to HLA-DQ3 + Alternaria-sensitive asthmatics including those with moderate-severe asthma (p < 0.02 and <0.003, respectively). CONCLUSIONS: In Alternaria-sensitive moderate-severe asthma, there is decreased frequency of HLA-DQ3 and increased IL-5 and IL-13 synthesis compared to Alternaria-sensitive mild asthmatics. HLA-DQ3 may be protective in development of Alternaria-sensitive moderate-severe asthma in children.
Full conference title:
American Academy of Allergy Asthma & Immunology