1. ¹Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK
2. ²Dermatology Centre, The University of Manchester, Manchester, UK

Correspondence: Dr Richard D.R. Camp, Department of Infection, Immunity and Inflammation, University of Leicester, Medical Sciences Building, University Road, Leicester LE1 9HN, UK. E-mail: rdrc1@le.ac.uk

Received 9 July 2007; Revised 13 February 2008; Accepted 20 February 2008; Published online 3 April 2008.

Abstract

Substantial evidence indicates that psoriasis is a T-lymphocyte-mediated autoimmune disease. However, longstanding data also indicate IgG and complement deposition in upper epidermis of psoriasis plaques. This led us to propose that autoantigen–autoantibody interactions in the skin may also be of pathogenic importance. Here, we have confirmed the presence of IgG in upper lesional epidermis and used high-resolution two-dimensional immunoblotting of extracts from this tissue, and laser desorption mass spectrometry of tryptic peptides, to define a series of epidermal proteins that bind IgG from psoriatic serum. The most prominent of these autoantigens are homologues of the serpin, squamous cell carcinoma antigen (SCCA), the other autoantigens identified including arginase 1, enolase 1, and keratin 10. Blood levels of IgG autoantibodies that bind to SCCA proteins were significantly higher in psoriasis than healthy controls (P=0.005), but were not detectable in sera from patients with active atopic dermatitis. To our knowledge, SCCA proteins have not previously been described as autoantigenic in animals or humans and form complexes with IgG that are associated with complement deposition. These findings expose potentially pathogenic humoral immunologic events and thus possible therapeutic targets in psoriasis.