Abstract
Pemphigus foliaceus (PF) is a human autoimmune disease in which antibodies are directed against the cell surface of epidermal cells with resultant blister formation. The histopathology of these blisters indicates that cells have detached from each other, and electron microscopy of early blisters shows diminished numbers, to complete loss, of desmosomes as well as abnormalities of the tonofilament- desmosome complex. In this study we demonstrate that autoantibodies from certain PF patients bind to a desmosomal core glycoprotein called desmoglein (DG) I. Proteins in extracts of normal human epidermis were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE), then transferred to nitrocellulose or 2- aminophenylthioether paper for immunoperoxidase staining. Results of these immunoblots indicated that sera from 6 of 13 PF patients specifically and intensely stained an approximately 160,000 mol wt polypeptide, "PF antigen". Such staining was not seen with normal human sera or sera from patients with pemphigus vulgaris or bullous pemphigoid, two autoimmune blistering skin diseases that are clinically, histologically, and immunochemically distinct from PF. However, rabbit antiserum directed against DGI, that was isolated from bovine muzzle desmosomes, stained a polypeptide band which co-migrated with PF antigen. Furthermore, when proteins from extracts of normal human epidermis were electrophoresed in two dimensions (isoelectric focusing, then SDS-PAGE) before transfer to nitrocellulose for immunoperoxidase staining, PF antibodies and antibodies to DGI stained identical spots. Finally, PF sera as well as PF IgG that was affinity purified with PF antigen from normal human epidermis, both selectively bound to DGI extracted from bovine muzzle desmosomes. These studies demonstrate that the human autoantibodies from certain patients with PF, a disease of epidermal cell adhesion, are directed against a desmosomal core protein.
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- Ames G. F., Nikaido K. Two-dimensional gel electrophoresis of membrane proteins. Biochemistry. 1976 Feb 10;15(3):616–623. doi: 10.1021/bi00648a026. [DOI] [PubMed] [Google Scholar]
- Anhalt G. J., Labib R. S., Voorhees J. J., Beals T. F., Diaz L. A. Induction of pemphigus in neonatal mice by passive transfer of IgG from patients with the disease. N Engl J Med. 1982 May 20;306(20):1189–1196. doi: 10.1056/NEJM198205203062001. [DOI] [PubMed] [Google Scholar]
- Beutner E. H., Jordon R. E., Chorzelski T. P. The immunopathology of pemphigus and bullous pemphigoid. J Invest Dermatol. 1968 Aug;51(2):63–80. [PubMed] [Google Scholar]
- Cohen S. M., Gorbsky G., Steinberg M. S. Immunochemical characterization of related families of glycoproteins in desmosomes. J Biol Chem. 1983 Feb 25;258(4):2621–2627. [PubMed] [Google Scholar]
- Cowin P., Garrod D. R. Antibodies to epithelial desmosomes show wide tissue and species cross-reactivity. Nature. 1983 Mar 10;302(5904):148–150. doi: 10.1038/302148a0. [DOI] [PubMed] [Google Scholar]
- Farb R. M., Dykes R., Lazarus G. S. Anti-epidermal-cell-surface pemphigus antibody detaches viable epidermal cells from culture plates by activation of proteinase. Proc Natl Acad Sci U S A. 1978 Jan;75(1):459–463. doi: 10.1073/pnas.75.1.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Franke W. W., Kapprell H. P., Mueller H. Isolation and symmetrical splitting of desmosomal structures in 9 M urea. Eur J Cell Biol. 1983 Nov;32(1):117–130. [PubMed] [Google Scholar]
- Franke W. W., Schmid E., Grund C., Müller H., Engelbrecht I., Moll R., Stadler J., Jarasch E. D. Antibodies to high molecular weight polypeptides of desmosomes: specific localization of a class of junctional proteins in cells and tissue. Differentiation. 1981;20(3):217–241. doi: 10.1111/j.1432-0436.1981.tb01178.x. [DOI] [PubMed] [Google Scholar]
- Gorbsky G., Cohen S., Steinberg M. S. Desmosomal antigens are not recognized by the majority of pemphigus autoimmune sera. J Invest Dermatol. 1983 Jun;80(6):475–480. doi: 10.1111/1523-1747.ep12534924. [DOI] [PubMed] [Google Scholar]
- Gorbsky G., Steinberg M. S. Isolation of the intercellular glycoproteins of desmosomes. J Cell Biol. 1981 Jul;90(1):243–248. doi: 10.1083/jcb.90.1.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hashimoto K., Lever W. F. An electron microscopic study on pemphigus vulgaris of the mouth and the skin with special reference to the intercellular cement. J Invest Dermatol. 1967 Jun;48(6):540–552. doi: 10.1038/jid.1967.86. [DOI] [PubMed] [Google Scholar]
- Hashimoto K., Shafran K. M., Webber P. S., Lazarus G. S., Singer K. H. Anti-cell surface pemphigus autoantibody stimulates plasminogen activator activity of human epidermal cells. A mechanism for the loss of epidermal cohesion and blister formation. J Exp Med. 1983 Jan 1;157(1):259–272. doi: 10.1084/jem.157.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones J. C., Arnn J., Staehelin L. A., Goldman R. D. Human autoantibodies against desmosomes: possible causative factors in pemphigus. Proc Natl Acad Sci U S A. 1984 May;81(9):2781–2785. doi: 10.1073/pnas.81.9.2781. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Morioka S., Naito K., Ogawa H. The pathogenic role of pemphigus antibodies and proteinase in epidermal acantholysis. J Invest Dermatol. 1981 May;76(5):337–341. doi: 10.1111/1523-1747.ep12519988. [DOI] [PubMed] [Google Scholar]
- Mueller H., Franke W. W. Biochemical and immunological characterization of desmoplakins I and II, the major polypeptides of the desmosomal plaque. J Mol Biol. 1983 Feb 5;163(4):647–671. doi: 10.1016/0022-2836(83)90116-x. [DOI] [PubMed] [Google Scholar]
- O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
- Peterson L. L., Wuepper K. D. Isolation and purification of a pemphigus vulgaris antigen from human epidermis. J Clin Invest. 1984 Apr;73(4):1113–1120. doi: 10.1172/JCI111297. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raknerud N. The ultrastructure of the interfollicular epidermis of the hairless (hr/hr) mouse. III. Desmosomal transformation during keratinization. J Ultrastruct Res. 1975 Jul;52(1):32–51. doi: 10.1016/s0022-5320(75)80020-7. [DOI] [PubMed] [Google Scholar]
- Schiltz J. R., Michel B., Papay R. Appearance of "pemphigus acantholysis factor" in human skin cultured with pemphigus antibody. J Invest Dermatol. 1979 Dec;73(6):575–581. doi: 10.1111/1523-1747.ep12541618. [DOI] [PubMed] [Google Scholar]
- Schiltz J. R., Michel B., Papay R. Pemphigus antibody interaction with human epidermal cells in culture. J Clin Invest. 1978 Oct;62(4):778–788. doi: 10.1172/JCI109189. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stanley J. R., Koulu L., Thivolet C. Distinction between epidermal antigens binding pemphigus vulgaris and pemphigus foliaceus autoantibodies. J Clin Invest. 1984 Aug;74(2):313–320. doi: 10.1172/JCI111426. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stanley J. R., Woodley D. T., Katz S. I. Identification and partial characterization of pemphigoid antigen extracted from normal human skin. J Invest Dermatol. 1984 Jan;82(1):108–111. doi: 10.1111/1523-1747.ep12259224. [DOI] [PubMed] [Google Scholar]
- Stanley J. R., Yaar M., Hawley-Nelson P., Katz S. I. Pemphigus antibodies identify a cell surface glycoprotein synthesized by human and mouse keratinocytes. J Clin Invest. 1982 Aug;70(2):281–288. doi: 10.1172/JCI110615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- WILGRAM G. F., CAULFIELD J. B., MADGIC E. B. AN ELECTRON MICROSCOPIC STUDY OF ACANTHOLYSIS AND DYSKERATOSIS IN PEMPHIGUS FOLIACEUS: WITH A SPECIAL NOTE ON PECULIAR INTRACYTOPLASMIC BODIES. J Invest Dermatol. 1964 Nov;43:287–299. doi: 10.1038/jid.1964.159. [DOI] [PubMed] [Google Scholar]
- White F. H., Gohari K. Desmosomes in hamster cheek pouch epithelium: their quantitative characterization during epithelial differentiation. J Cell Sci. 1984 Mar;66:411–429. doi: 10.1242/jcs.66.1.411. [DOI] [PubMed] [Google Scholar]
- Woo T. Y., Hogan V. A., Patel H., Anhalt G. J., Labib R. S., Voorhees J. J., Diaz L. A. Specificity and inhibition of the epidermal cell detachment induced by pemphigus IgG in vitro. J Invest Dermatol. 1983 Jul;81(1 Suppl):115s–121s. doi: 10.1111/1523-1747.ep12540871. [DOI] [PubMed] [Google Scholar]