Translational Research in Psoriasis.

Translational research is a coordinated process that converts scientific knowledge about diseases from basic research into the development of therapeutic or diagnostic procedures in order to improve public health. Recent insights into the pathogenesis of psoriasis have greatly promoted the rational development of new therapeutic approaches. The integration of genetic predisposition and pathogenetic events defined the cytokine cascade as a target for therapeutic interventions. Applying various phases of translational research has enabled development of novel therapies that combine high efficacy with convincing safety profiles, with important implications for public health.

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

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.

Effect of calcipotriol on etanercept partial responder psoriasis vulgaris and psoriatic arthritis patients.

Patients who respond only partially to etanercept may require additional treatments that act synergistically to improve their therapeutic response while at the same time reducing the dose required and the risk of side-effects. The aim of this study was to evaluate the effecti veness of topical calcipotriol in etanercept partial responder patients. We enrolled 120 patients affected by psoriasis vulgaris and psoriatic arthritis. A 50 mg dose of etanercept was administered twice weekly for the first 12 weeks, followed by a 25 mg dose twice weekly for an additional 12 weeks. At week 12, for 45 patients who had not achieved PASI 50, calcipotriol cream was also prescribed twice daily for 4 weeks and then once daily for a further 8 weeks. At week 24, of the 45 patients in the group treated with etanercept plus calcipotriol, 14 (31.1%) had achieved PASI 75, and 23 PASI 50, while 8 (17.7%) had dropped out of therapy; of the 75 patients who continued etanercept in monotherapy with a 25 mg dose twice weekly for another 12 weeks, 71 (94.6%) had achieved PASI 50 and 57 (76.0%) PASI 75. The application of calcipotriol in etanercept partial responder patients had therefore helped 37 out of 120 patients (31%) achieve at least PASI 50. This is the first report about the controlled combination of topical calcipotriol and etanercept in a large group of psoriatic patients. The efficacy and cost-effectiveness of the combined treatment is evidenced by the good response shown at week 24 by a group of etanercept low-responder patients using drugs sparingly and limiting likely toxicity.

Photodynamic therapy for granuloma annulare: more than a shot in the dark.

BACKGROUND: Granuloma annulare (GA) is a benign granulomatous and inflammatory skin disorder. The pathogenesis remains enigmatic and convincingly effective treatment options are not available. Inspired by a report showing photodynamic therapy (PDT) to be effective in a single patient with GA, we sought to evaluate this benefit in a series of patients with GA. OBSERVATIONS: PDT was performed in 7 consecutive patients with histologically confirmed GA located at the extremities. First, 20% ALA gel was applied under an occlusive dressing for 5 h, followed by illumination with 100 J/cm(2) by a standard red-light source. In total, 2-3 PDT sessions were performed, with an interval of 2-4 weeks between each session. Treatment was stopped when complete remission was achieved or when GA lesions remained unchanged after 2 consecutive PDT sessions. The overall response rate was 57%. In 2 patients (29%), GA cleared completely, in 2 patients (29%) the skin lesions improved markedly and in 3 patients (43%) no clinical response could be observed. CONCLUSION: These promising results should be evaluated in larger controlled studies. In selected patients, PDT might be a valuable recruit for the sparse armory available to treat GA.

Detection of the 47-kilodalton membrane immunogen gene of Treponema pallidum in various tissue sources of patients with syphilis.

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.