Ezrin, maspin, peroxiredoxin 2, and heat shock protein 27: potential targets of a streptococcal-induced autoimmune response in psoriasis

• Published in: The Journal of immunology (1950) 2010-05, Vol.184 (9), p.5392-5402
• Main Authors: Besgen, Petra, Trommler, Paul, Vollmer, Sigrid, Prinz, Joerg Christoph
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Autoantigens - immunology; Autoimmune Diseases - blood; Autoimmune Diseases - immunology; Autoimmune Diseases - microbiology; Cell Line, Transformed; Cell Line, Tumor; Cells, Cultured; Cytoskeletal Proteins - blood; Cytoskeletal Proteins - immunology; Epitopes, T-Lymphocyte - immunology; HSP27 Heat-Shock Proteins - blood; HSP27 Heat-Shock Proteins - immunology; Humans; Keratinocytes - immunology; Keratinocytes - metabolism; Keratinocytes - pathology; Molecular Sequence Data; Peroxiredoxins - blood; Peroxiredoxins - immunology; Psoriasis - blood; Psoriasis - immunology; Psoriasis - microbiology; Rabbits; Serpins - blood; Serpins - immunology; Streptococcal Infections - blood; Streptococcal Infections - immunology; Streptococcal Vaccines - administration & dosage; Streptococcal Vaccines - immunology; Streptococcus pyogenes - immunology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - microbiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0903520

Psoriasis is an HLA-Cw6-associated T cell-mediated autoimmune disease of the skin that is often triggered by streptococcal angina. To identify keratinocyte proteins, which may become psoriatic autoantigens as the result of an immune response against streptococci, rabbits were immunized with heat-killed Streptococcus pyogenes. Streptococcal immunization induced Ab formation against various human keratinocyte proteins. Sera from psoriasis patients reacted against several of these proteins as well. Common serologic reactivities of rabbits and patients included the proteins ezrin, maspin, peroxiredoxin 2 (PRDX2), heat shock protein (hsp)27, and keratin 6. When used for stimulation of blood lymphocytes, ezrin, maspin, PRDX2, and hsp27 induced increased T cell activation in psoriasis patients, which was particularly evident for HLA-Cw6(+) individuals. Ag-specific T cell lines generated with these proteins consisted predominantly of CD8(+) T cells and used TCR beta-chain rearrangements, which were highly homologous to those expanded within the corresponding skin lesion. Several immunodominant epitopes on the different proteins could be defined according to sequence alignments with the whole genome of S. pyogenes. Our data indicate that maspin, ezrin, PRDX2, hsp27, and potentially keratin 6 could act as autoantigens of a streptococcal-induced autoimmune response and represent targets of the exaggerated T cell response in psoriasis. Additionally, ezrin and hsp27 might constitute antigenic links between psoriasis and inflammatory bowel disease, uveitis, or arteriosclerosis, which are clinically associated.