Humoral Autoimmune Responses to the Squamous Cell Carcinoma Antigen Protein Family in Psoriasis

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.

Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancer and in patients with cancer of unknown primary site

“…Our results suggest that serum CA 125 levels differ according to the type of effusion, with significantly higher concentrations in patients with ascites and different cut points may be used according to the effusion type. However, other tumor markers, such as SCC, show indistinguishable concentrations in some conditions such as renal failure or dermatological disorders and patients with these pathologies may be excluded [36,37]. Using these criteria, our specificity was individually higher than 98.9%, and using all tumor markers, it was also high-97.5%.…”

Protective Vaccination against Papillomavirus-Induced Skin Tumors under Immunocompetent and Immunosuppressive Conditions: A Preclinical Study Using a Natural Outbred Animal Model

“…Firstly, although poorly understood, the skin can be infiltrated by a subset of B cells that connect innate with adaptive immunity [49]. Secondly, high-resolution two-dimensional immunoblotting assays revealed the presence of IgGs in the upper lesional epidermis of psoriasis plaques [50], also known to be positive for cutaneous HPV types [51]. It remains to be determined how the exact spatial-temporal mechanism(s) that finally protects against a papillomavirus infection in the skin operates.…”

Autoantibodies in Scurfy Mice and IPEX Patients Recognize Keratin 14

“…Using a similar approach as we did, one study previously identified keratin 10-specific antibodies in sera of psoriasis patients by protein identification (El-Rachkidy et al ., 2008). Another recent study reported anti-keratin autoantibodies in patients with rheumatoid arthritis (Quismorio et al ., 2008).…”