Autoantibodies in the Extraintestinal Manifestations of Celiac Disease

Increased antibody reactivity towards self-antigens is often indicative of a disruption of homeostatic immune pathways in the body. In celiac disease, an autoimmune enteropathy triggered by the ingestion of gluten from wheat and related cereals in genetically predisposed individuals, autoantibody reactivity to transglutaminase 2 is reflective of the pathogenic role of the enzyme in driving the associated inflammatory immune response. Autoantibody reactivity to transglutaminase 2 closely corresponds with the gluten intake and clinical presentation in affected patients, serving as a highly useful biomarker in the diagnosis of celiac disease. In addition to gastrointestinal symptoms, celiac disease is associated with a number of extraintestinal manifestations, including those affecting skin, bones, and the nervous system. Investigations of these manifestations in celiac disease have identified a number of associated immune abnormalities, including B cell reactivity towards various autoantigens, such as transglutaminase 3, transglutaminase 6, synapsin I, gangliosides, and collagen. Clinical relevance, pathogenic potential, mechanism of development, and diagnostic and prognostic value of the various identified autoantibody reactivities continue to be subjects of investigation and will be reviewed here.