Research of disease selective immunotherapy in autoimmune diseases

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Pemphigus is a life-threatening autoimmune blistering disease of the skin and mucous membranes. In patients with pemphigus, circulating autoantibodies against cell surface of keratinocytes in stratified squamous epithelia play a pathogenic part, and cause loss of cell-cell adhesion with resultant blister formation. Since the detection of autoantibodies by indirect immunofluorescence in canine pemphigus is usually difficult probably due to the low sensitivity of the substrate, several substrates for immunofluorescence were studied. As a result, bovine esophagus showed highest sensitivity and specifity. For investigating the autoantigens directed by the serum of pemphigus foliaceus, cloning and sequencing of canine desmoglein 1 (Dsg1) were performed using cDNA library from canine skin. Fusion proteins of Dsg1 expressed in baculovirus were made. These proteins reacted with sera from human patients with pemphigus foliaceus, suggesting that canine Dsg1 crossreacted with human autoantibodies from pemphigus foliaceus. ELISPOT (enzyme-linked immunospot assay) was developed for the detection of antigen-specific B cells in patients with pemphigus. This method will provide us to analyze frequencies of Dsg-specific IgG producing and memory B cells.