Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1391
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - Jun 19 2019

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Pemphigus
Autoantigens
Keratinocytes
Catenins
Immunoblotting
Antigens
Desmogleins
Desmoglein 3
Desmoglein 1
Monoclonal Antibodies
Blister
Surface Antigens
Immunoprecipitation
Recombinant Proteins
Autoantibodies
Autoimmune Diseases
Anti-Idiotypic Antibodies
Mucous Membrane
B-Lymphocytes
Immunoglobulin G

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Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris. / Di Lullo, Giulia; Calabresi, Valentina; Mariotti, Feliciana; Zambruno, Giovanna; Lanzavecchia, Antonio; Di Zenzo, Giovanni.

In: Frontiers in Immunology, Vol. 10, 19.06.2019, p. 1391.

Research output: Contribution to journalArticle

Di Lullo, Giulia ; Calabresi, Valentina ; Mariotti, Feliciana ; Zambruno, Giovanna ; Lanzavecchia, Antonio ; Di Zenzo, Giovanni. / Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris. In: Frontiers in Immunology. 2019 ; Vol. 10. pp. 1391.
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AB - 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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