The Protease Inhibitor Alpha-2-macroglobulin-like-1 is the P170 Antigen Recognized by Paraneoplastic Pemphigus Autoantibodies in Human

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2010 Sep 1

PMID 20805888

Citations 36

Authors

Isabelle Schepens

Fabienne Jaunin

Nadja Begre

Ursula Laderach

Katrin Marcus

Takashi Hashimoto

Bertrand Favre

Luca Borradori

Affiliations

Soon will be listed here.

Abstract

Background: Paraneoplastic pemphigus (PNP) is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, and associated with underlying neoplasms. PNP is characterized by the production of autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion. Nevertheless, the identity of an antigen of Mr 170,000 (p170), thought to be critical in PNP pathogenesis, has remained unknown.

Methodology/principal Findings: Using an immunoprecipitation and mass spectrometry based approach, we identified p170 as alpha-2-macroglobuline-like-1, a broad range protease inhibitor expressed in stratified epithelia and other tissues damaged in the PNP disease course. We demonstrate that 10 PNP sera recognize alpha-2-macroglobuline-like-1 (A2ML1), while none of the control sera obtained from patients with bullous pemphigoid, pemphigus vulgaris, pemphigus foliaceus and normal subjects does.

Conclusions/significance: Our study unravels a broad range protease inhibitor as a new class of target antigens in a paraneoplastic autoimmune multiorgan syndrome and opens a new challenging investigation avenue for a better understanding of PNP pathogenesis.

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