Identification of a novel non-desmoglein autoantigen in Pemphigus Vulgaris

Di Lullo, Giulia; Calabresi, Valentina; Mariotti, Feliciana; Zambruno, Giovanna; Lanzavecchia, Antonio; Di Zenzo, Giovanni

doi:10.3389/fimmu.2019.01391

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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

19.06.2019

Published in:

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.

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