PURIFICATION OF FIBROBLAST-DERIVED CELIAC-DISEASE AUTOANTIGEN MOLECULES

We have recently purified autoantigen polypeptides reacting with celia c disease patient sera IgA from the extracellular noncollagenous matri x compartment of fetal lung tissue. These molecules trigger the produc tion of different tissue antibodies, the so-called antireticulin and a ntiendomysium antibodies in celiac disease. In the present report, we show that fibroblasts synthesize and secrete celiac disease autoantige n molecules. The secretion product, reactive with IgA from celiac dise ase patients, is a large-molecular-weight protein aggregate. When the protein complex was treated with 4 M guanidinium hydrochloride and 0.1 % SDS, 11 monocomponent polypeptides could be detected by PAGE. Of th ese, four single polypeptides with molecular weights of 17 000-39 500 and isoelectric points of 5.0-7.0 were observed to react with IgA sepa rated from sera of children with celiac disease. The polypeptide molec ules produced by fibroblasts in vitro bound to antireticulin and antie ndomysium antibodies but not to antigliadin antibodies. The present ob servations show that tissue antibodies found to be specifically associ ated with celiac disease are generated against a synthesis product of fibroblasts, a cell-type known to synthesize a number of biologically active polypeptides. The fibroblast-derived extracellular matrix prote ins and the formed autoantibodies may be important in the pathogenesis of gluten-sensitive enteropathy.