Asthma and HLA system.

Abstract

Study of atopic asthma provides an excellent model for our understanding of the complex molecular genetics of human immune responsiveness. Family and population studies have suggested that multiple genetic factors influence global and specific immune responsiveness to allergens. Global response of IgE production appears to be controlled by a dominant "atopy gene" unlinked to HLA class II associated Ir genes, whereas the specific immune response in terms of IgE and IgG antibodies against precise allergens is unequivocally linked to the HLA class II molecules. Other genetic factors/polygenic component may influence the bronchial hyperreactivity observed among asthmatics. Not the least, the genetics of the "releasability" of mediators of inflammation from basophils should also be considered in the genetic studies of asthma. Given this overall complexity of genetics of asthma, we primarily focused our attention to the genetics of a defined subgroup of asthmatic patients. We have chosen to study three well-defined clinical subsets (atopic asthma with and without aspirin sensitization, and nonatopic asthma with aspirin sensitization) in comparison to age and sex matched control groups for their HLA class II polymorphism at the DNA level. Use of in vitro DNA amplification and allele specific restriction enzymes allowed us to define that a particular combination of a specific DQ and DPB alleles is highly prevalent among asthmatic patients with aspirin sensitization and this is exclusively in an atopic context (R.R. = 54). Intriguingly, an identical combination of HLA alleles are similarly enriched among patients with coeliac disease. Further studies are required to understand such an intriguing similarities of molecular markers between these apparently two unrelated disorders.