An aim of the musculoskeletal component of the BRC has been the collection of data on cytokine production and alternations in T lymphocyte subsets in patients with inflammatory arthritis. There has been considerable interest in newly identified T cell subsets in the last 5-10 years, particularly T cells with regulatory capacities and those which make the cytokine IL-17, which has been implicated in a number of animal models of inflammatory arthritis. In patients with ankylosing spondylitis we have characterised an expanded population of CD8+ T cells with potent regulatory functions, and we are investigating the pathogenetic role of this subset. It may represent an inflammation-induced negative feedback mechanism; whilst this is clearly not effective since patients continue to have active inflammation, it is a mechanism that might be exploited therapeutically.
We were the first laboratory to document increased numbers of T cells making IL-17 in peripheral blood of patients with ankylosing spondylitis and in the related condition of reactive arthritis. The phenotype of these cells, and the other cytokines they produce, has been investigated together with their presence at the site of inflammation. These findings have led to additional studies on factors driving the differentiation and expansion of IL-17 producing T cells. These observations are timely in view of the availability of therapeutic antibodies to both IL-17 and the principal IL-17-driving cytokine, IL-23, and rational use of these therapies will be guided by the observations we have made.
These studies were greatly facilitated by the BRC, which enables us to obtain blood and synovial fluid samples from well characterized patients in routine clinics and to perform phenotyping studies of the kind outlined above. This approach will be continued and extended to other components of the BRC through the opening of the immunophenotyping hub in 2011.
