ABSTRACT
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.
Subject(s)
Autoimmune Diseases/immunology , Autoimmune Diseases/microbiology , Cytoskeletal Proteins/immunology , HSP27 Heat-Shock Proteins/immunology , Peroxiredoxins/immunology , Psoriasis/immunology , Serpins/immunology , Streptococcal Infections/immunology , Amino Acid Sequence , Animals , Autoantigens/immunology , Autoimmune Diseases/blood , Cell Line, Transformed , Cell Line, Tumor , Cells, Cultured , Cytoskeletal Proteins/blood , Epitopes, T-Lymphocyte/immunology , HSP27 Heat-Shock Proteins/blood , Humans , Keratinocytes/immunology , Keratinocytes/metabolism , Keratinocytes/pathology , Molecular Sequence Data , Peroxiredoxins/blood , Psoriasis/blood , Psoriasis/microbiology , Rabbits , Serpins/blood , Streptococcal Infections/blood , Streptococcal Vaccines/administration & dosage , Streptococcal Vaccines/immunology , Streptococcus pyogenes/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/microbiologyABSTRACT
Polymerase chain reaction (PCR) was used to detect the 47-kDa immunogen gene of Treponema pallidum in peripheral blood mononuclear cells (PBMCs), skin lesions, and serum, but less consistently in purified granulocytes or ejaculates of patients with manifest and latent syphilis. Therefore, skin lesions and PBMCs may serve as the most reliable sources for a PCR-based diagnosis of syphilis.