HLA and gluten

    HLA genes produce a group of proteins called the human leukocyte antigen complex, which is responsible for how the immune system distinguishes between the body’s own proteins and foreign, potentially harmful proteins. Variations in HLA genes can be used to assess the risk of gluten intolerance. Approximately 99% of people with celiac disease and 60% of people with non-celiac gluten sensitivity (NCGS) have the risk version DQ2 or DQ8 of HLA.

     Gliadin, a component of gluten, a protein found in wheat, barley and rye, has the ability to bind to the chemokine receptor CXCR3 (expressed on intestinal epithelial cells), especially in individuals with non-celiac gluten sensitivity, and induce MYD88-dependent activation of the zonulin pathway. Failure to do so increases intestinal permeability, allowing antigens to pass into the bloodstream. 

    Genetic predisposition, miscommunication between innate and adaptive immunity, exposure to environmental triggers, and loss of intestinal barrier function secondary to activation of the zonulin pathway by food-derived environmental triggers or alterations in the gut microbiota appear to be key ingredients involved in the pathogenesis of inflammation.