Celiac.com 05/30/2016 - People with HLA genes have the highest risk factor for developing autoimmune disorders. The vast majority of people with celiac disease carry the HLA DQA1*05 and DQB1*02 alleles, both of which encode the DQ2.5 molecule.
In order to activate pathogenic CD4+ T lymphocytes, that is, to trigger active celiac disease, it is necessary for the body to form complexes between DQ2.5 and gluten peptides on antigen-presenting cells (APCs). It is widely accepted by clinicians that the DQ2.5 genes establish the different intensities of anti-gluten immunity, depending on whether they are in a heterozygous or a homozygous configuration, that is, whether both genes are activated, or only one gene is activated.
The research team's recent study shows that, in celiac patients, HLA DQA1*05 and DQB1*02 gene expression is much higher than expression of non-celiac-associated genes. This, in turn, impacts protein levels and causes a comparable cell surface exposure of DQ2.5 heterodimers between DQ2.5 homozygous and heterozygous celiac patients. As a consequence, the magnitude of the anti-gluten CD4+ T cell response is strictly dependent on the antigen dose, and not on the DQ2.5 gene configuration of APCs.
These findings are important, because they support the idea that the expression of DQ2.5 genes is an important risk factor in celiac disease.
The preferential expression of DQ2.5 alleles observed in this study offers a new explanation of why these genes are so frequently associated with celiac disease and with other autoimmune disorders.