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 the 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, pathogenesis and determination of the patients' eligibility to enter experimental therapeutic protocols. Patients are asked to contribute blood, skin and/or synovial membrane samples for immunologic research studies. Immunologic studies include investigations of 1) relative importance of monocyte and T cell-derived cytokines in the disease process; and 2) biology and role of metalloproteinases and angiogenesis in this disease. Results: Using immunohistochemistry, we studied the expression and activity of monocyte-derived cytokines in synovial samples from patients with psoriatic arthritis and compared it to synovial samples of patients with rheumatoid arthritis. Common pathways were evident in the synovial immune responses in PsA and RA, such as the presence of TNFa, IL-1 and activation of NF?B, but subtle differences exist. We found lower number of lining layer macrophages in PsA and reduced expression of TNFa, IL-1? and IL-15. IL-10 was identified at equivalent levels in RA and PsA, however, a higher median TNFa /IL-10 ratio was present in PsA. These data together with previous data from our group supporting oligoclonal T-cell expansions clearly suggest, that compared to RA, PsA is more likely a T-cell dependent, antigen driven disease. The study also demonstrated that even if inciting events in PsA and RA are different, synovial responses ultimately share common pathways including, at least, TNFa and IL-1 and likely other inflammatory mediators. Novel biologic strategies to treat PsA can be based on our better understanding of the underlying pathogenic mechanisms. Lay Summary: Psoriasis 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 inflammatory cells and their products in causing this disease. Thus far we have demonstrated that certain inflammatory cells called T lymphocytes and monocytes, are present in the inflamed joints and are important contributors of the inflammatory process. In addition, we have identified several molecules produced by these cells that cause inflammation and could be targets for future therapy.
| 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 |
