Thompson, Paul Warren; (1990) Cytidine deaminase in rheumatoid arthritis. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Cytidine deaminase (CD) is an cytoplasmic enzyme found in high concentrations in polymorphonuclear leucocytes (polymorphs). In rheumatoid arthritis (RA) huge numbers of polymorphs are attracted to inflamed joints where they lyse releasing their contents into synovial fluid. The thesis describes a series of experiments designed to test the hypothesis that, in RA, CD drains from synovial fluid to blood where serum levels represent an integrated measure of 'acute' inflammation. An assay was established and evaluated. Studies of CD in joint tissues and body fluids showed that serum levels of CD were raised in RA patients with a gradient running from synovial polymorphs to synovial fluid, across the synovium to blood. The mean synovial fluid CD level was very close to the value predicted using a mathematical model of synovial fluid solute kinetics. Studies of a variety of other enzymes and a selective inhibitor of CD supported the joint polymorph as the source of origin for serum CD in RA. Clinical evaluation revealed a small diurnal variation in serum CD in RA patients probably related to exercise increasing lymphatic drainage from joints. Serum CD was shown to correlate cross-sectionally and longitudinally with other clinical and biochemical measures of joint inflammation in RA, and levels were able to detect the flare produced by the withdrawal of non-steroidal anti-inflammatory drugs from RA patients. The results were discussed according to the principles of measurement theory. In conclusion, serum CD is a simple, cheap, reproducible and sensitive measure of joint inflammation in RA that reflects polymorph lysis known to be at the centre of the inflammatory process. It supplies the clinician with a serological tool for patient monitoring which is a direct assessment of one aspect of inflammation.

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