Pemphigus is an
autoimmune disease that causes blistering of human epidermis. We have recently shown that
autoantibodies in the serum of three
pemphigus patients bind to desmosomes (Jones, J. C. R., J. Arnn, L. A. Staehelin, and R. D. Goldman, 1984, Proc. Natl. Acad. Sci. USA., 81:2781-2785), and we suggested that
pemphigus blisters form, at least in part, from a specific antibody-induced disruption of desmosomes in the epidermis. In this paper, experiments are described that extend our initial observations. 13
pemphigus serum samples, which include four known
pemphigus vulgaris (Pv) and four known
pemphigus foliaceus (Pf) serum samples, have been analyzed by both immunofluorescence and by immunoblotting using cell-free desmosome preparations. Tissue sections of mouse skin processed for double indirect immunofluorescence using each of the
pemphigus serum samples and a rabbit antiserum directed against a component of the desmosomal plaque (
desmoplakin) show similar punctate cell surface staining patterns. This suggests that all 13
pemphigus serum samples contain
autoantibodies that recognize desmosomes. These
autoantibodies appear specific for stratified squamous epithelial cell desmosomes and do not recognize desmosomes of other tissues (e.g., mouse heart and mouse intestine). Cultured mouse keratinocytes, which possess well-defined desmosomes, were processed for indirect immunofluorescence using the
pemphigus serum samples. Eight of the 13 sera (including the four known Pv samples but not the known Pf sera)
stain desmosomes in these preparations. By double indirect immunofluorescence the
desmoplakin antiserum stains a double fluorescent line along the contacting edges of cultured keratinocytes, whereas the positive
pemphigus serum samples
stain a single fluorescent line along this same border. We believe that these
pemphigus autoantibodies recognize extracellular
antigens located somewhere within the region between the two apposing membranes that comprise the desmosome. The
pemphigus sera exhibit positive immunoblotting reactions with desmosome-enriched fractions obtained from bovine tongue epithelium. Three serum samples (including two of the four known Pf serum samples) react with 160- and 165-kD desmosome-associated
polypeptides (Koulu, L., A. Kusimi, M. S. Steinberg, V. Klaus-Kovtun, and J. R. Stanley, 1984, J. Exp. Med., 160:1509-1518). Another eight serum samples (including the four known Pv sera) recognize a 140-kD desmosome-associated
polypeptide. We propose that the
antigens recognized by these human
autoantibodies may play important roles in the adhesion of cells within the epidermis.(ABSTRACT TRUNCATED AT 400 WORDS)