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Front Immunol. 2019 Jun 19;10:1391. doi: 10.3389/fimmu.2019.01391. eCollection 2019.

Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris.

Author information

1
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.
2
Laboratory of Molecular and Cell Biology, IDI-IRCCS, Rome, Italy.
3
Genetic and Rare Diseases Research Division, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
4
Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.

Abstract

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.

KEYWORDS:

autoantibodies; memory B cells; mucous membranes; non-desmoglein autoantigens; pemphigus vulgaris; skin; α-catenin

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