Background and Objective: These studies are targeted towards understanding the pathogenesis of psoriatic arthritis and the development of specific immunotherapies for psoriatic arthritis, a relatively common chronic inflammatory disease affecting skin and joints. Patients with known or suspected psoriatic arthritis are evaluated at the Clinical Center. Studies include characterization of the clinical and laboratory features of the disease, research studies of the natural history and pathogenesis and determination of the patients eligibility to enter experimental therapeutic protocols. Patients are asked to contribute blood, skin or synovial membrane samples for immunologic research studies. Immunologic studies include investigations of 1) T cell antigen receptor (TCR) repertoire in the peripheral blood and at sites of inflammation (i.e., skin and joints); 2) relative importance of monocyte and T cell-derived cytokines in the disease process; and 3) biology and role of metalloproteinases and angiogenesis in this disease. Results our investigations on TCR repertoire analysis and cytokine regulation were reported last year. Angiogenesis and metalloproteinase expression. Using immunohistochemistry and zymography we studied the expression and activity of metalloproteinases (MMPs) in synovial samples and skin tissues from patients with psoriatic arthritis and compared it to synovial samples of patients with rheumatoid arthritis. The overall pattern of MMP expression was similar in the synovial lining and sublining layers in both diseases. A trend to greater MMP14 expression was seen in psoriatic synovium compared to the rheumatoid synovium. However, MMP2 (gelatinase) activity was comparable in both diseases. Analysis of skin revealed lower levels of MMP3, MMP14 and MMP15 compared to psoriatic synovium. These data provide the first comprehensive study of MMP expression and localization in psoriatic synovium and skin and demonstrate the presence of active MMPs at levels comparable to those found in patients with rheumatoid arthritis. The availability of selective inhibitors of metalloproteinases and other angiogenic molecules provides for the first time the opportunity to examine their role in the pathogenesis of disease in humans.Lay SummaryPsoriasis is a common inflammatory disease of the skin that affects approximately 2% of the population of the USA. Psoriasis is accompanied by a destructive arthritis in 5-15% of patients. Our studies examine the relative contribution of certain types of blood cells and their products in causing this disease. Thus far we have established an important role of certain blood cells called T lymphocytes and monocytes in causing inflammation. In addition, we have identified several molecules produced by these cells that cause inflammation which could be targets for future therapy. - Pathogenesis, Natural History, Psoriatic Arthritis, T cell antigen receptor, cytokine, metalloproteniases and angiogenesis - Human Subjects
| Takada, K; Danning, C L; Kuroiwa, T et al. (2003) Lymphocyte depletion with fludarabine in patients with psoriatic arthritis: clinical and immunological effects. Ann Rheum Dis 62:1112-5 |
