Molecular dissection of the tissue transglutaminase antoantibody response in celiac disease

Celiac disease (CD) is an intestinal malabsorption characterized by intoler ance to cereal proteins accompanied by immunological responses to dietary g liadins and tissue transglutaminase, an autoantigen located in the endomysi um. Tissue transglutaminase belongs to the family of enzymes that catalyze protein cross-linking reactions and is constitutively expressed in many tis sues as well as being activated during apoptosis, The role of gliadins in e liciting the immune response in CB and holy transglutaminase is linked to t he primary reaction are still unclear, In this work, we report the producti on and analysis of six phage Ab libraries from the peripheral and intestina l lymphocytes of three CD patients, We were able to isolate Abs to transglu taminase from all intestinal lymphocytes libraries but not from those obtai ned from peripheral lymphocytes, This is in contrast to Abs against gliadin , which could be obtained from all libraries, indicating that the humoral r esponse against transglutaminase occurs at the local level, whereas that ag ainst gliadin occurs both peripherally and centrally, Abs from all three pa tients recognized the same transglutaminase epitopes with a bias toward the use of the V(H)5 Ab variable region family, The possible role of these ant i-transglutaminase Abs in the onset of CD and associated autoimmune patholo gies is discussed.