Journal article

Identification of a novel non-desmoglein autoantigen in Pemphigus Vulgaris

  • Di Lullo, Giulia Tumor Immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy
  • Calabresi, Valentina Laboratory of Molecular and Cell Biology, IDI-IRCCS, Rome, Italy
  • Mariotti, Feliciana Laboratory of Molecular and Cell Biology, IDI-IRCCS, Rome, Italy
  • Zambruno, Giovanna Genetic and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
  • Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Di Zenzo, Giovanni Laboratory of Molecular and Cell Biology, IDI-IRCCS, Rome, Italy
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  • Frontiers in immunology. - 2019, vol. 10, p. 1391
English Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes characterized by the presence of circulating and tissue-bound autoantibodies against keratinocyte cell surface antigens, specifically desmoglein (Dsg) 1 and 3. The pathogenic role of anti-Dsg antibodies is well-established, while the mechanism of blister formation is only partly defined. We have applied a previously developed method for the efficient immortalization of IgG+ memory B cells to identify novel target antigens in PV. A human monoclonal antibody reactive with a hitherto unreported non-Dsg antigen was isolated. Immunoprecipitation and immunoblotting studies with keratinocyte extracts indicated α-catenin as the putative antigen, then confirmed by immunoblotting on the recombinant protein. Four of ten PV sera reacted with recombinant α- catenin. Although the isolated human monoclonal antibody was per se unable to dissociate keratinocyte monolayers and also to synergize with a pathogenic antibody in vitro, further studies are warranted to assess its possible in vivo contribution in the multifactorial pathogenesis and heterogeneous manifestations of PV disease.
  • English
Pathology, clinical medicine
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