Celiac disease (gluten intolerance) and Sjogren's syndrome (ocular component is 'Dry eye') are autoimmune diseases in which patients develop antibodies to the wheat storage protein a-gliadin. Both diseases affect epithelial cells (intestinal epithelial for Celiac disease; lacrimal acinar for the ocular component of Sjogren's syndrome) which have in common an intimate basal association with a thin extracellular matrix known as """"""""basement membrane"""""""". In a functional screen for basement membrane component(s) which might be required for normal lacrimal acinar cell secretory function the principal investigator's lab identified a novel 180 kDa cell adhesive protein, BM180, whose N-terminus shared sequence identity with a-gliadin. This unusual observation, made by foreign investigator while a visiting associate in the PIs lab, was reinforced by reactivity of monoclonal anti-a-gliadin antibodies with a 180 kDa protein in basement membrane and by high stringency hybridization of a-gliadin cDNA with genomic human, mouse and rat DNA, and with lacrimal mRNA of 2.3 kb. A logical extension of these data is that BM180 is an autoantigen in these two common diseases - particularly Celiac disease where circulating anti-a-gliadin antibodies have received more attention. Building on past collaborations and the expertise of the foreign collaborator, this project proposes to: (1) purify and characterize mouse BM180 using HPLC and capillary electrophoresis, and (2) initiate studies examining BM180-intestinal cell interactions.
