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Title: Complement mediated prevention of immune precipitation in rheumatic disease
Author: Mitchell, William Smith
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1988
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The prevention of immune complex precipitation (PIP) is the phenomenon whereby immune complexes formed at or near equivalence in serum are held in solution and an immune precipitate does not form. PIP is mediated by the complement system via activation of the classical pathway. The formation and deposition of circulating immune complexes is an important cause of immunologically mediated tissue injury. The complement system through the PIP mechanism therefore acts to prevent the formation of these large insoluble complexes which might deposit in tissues and thereby cause disease. My hypothesis was that if PIP was important in inhibiting the formation of these phlogistic complexes then one might expect there to be defects in PIP in patients with immune complex disease. I therefore developed an assay and proceeded to measure PIP in the sera of patients with rheumatic disease in which immune complexes were implicated in disease pathogenesis. The sera of forty seven per cent of patients with seropositive rheumatoid arthritis (RA) failed to prevent the precipitation of antigen-antibody complexes. This was not due to hypocomplementaemia suggesting that the impairment of PIP in these sera was due to the presence of an inhibitor of PIP. An assay to measure this inhibitory activity was developed. Inhibitory activity was found in the majority of patients with seropositive RA in both sera and synovial fluid. Sera from patients with seronegative arthritis contained little or no inhibitory activity. In seropositive RA sera inhibitory activity was inversely correlated with PIP. Inhibitory activity in the serum did not correlate with indices of generalised disease activity (articular index, erythrocyte sedimentation rate (ESR), haemoglobin, white cell count or platelet).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available