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Title: Immunological mechanisms in cardiac disease
Author: Harcombe, Alun Andrew
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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The aim of the work presented in this thesis was to examine cell and antibody-mediated immune mechanisms in heart muscle disease. The two conditions studied were acute rejection of cardiac allografts as an example of cell-mediated immune damage, and alcoholic heart muscle disease as a potential example of antibody-mediated disease. In the first study, experiments were performed on 94 endomyocardial biopsies (EMB) from 73 patients to determine the relationship between the ability to grow lymphocytes from EMB in culture and (i) grade of concurrent or future rejections, (ii) the presence of endocardial lymphocytic infiltrates (ELI), and (iii) donor/recipients HLA mismatches. These studies showed that outgrowth of lymphocytes was not closely related to the degree of rejection, not influenced by the use of polyclonal activators in the medium but it was affected by the presence to two HLA mismatches at the DR locus. The presence of ELI was related to rejection but not to outgrowth of the lymphocytes. It was concluded that, contrary to predictions in the literature, the ability to grow lymphocytes from EMB did not indicate presence of impending injection. In the second study, experiments were performed to test the hypothesis that alcoholic heart muscle disease may be caused by autoantibodies to acetaldehyde-modified myocardial proteins. Sera from 61 subjects were tested by Western analysis for antibodies against acetaldehyde-treated human myocardial proteins. No such antibodies were detected in 11 healthy controls subjects, or 28 patients with non-alcoholic heart diseases. In contrast, 4 out of 14 patients with alcoholic heart disease (28%) had detectable antibodies, suggesting a role for these antibodies in alcohol-induced heart muscle disease. To isolate potential antigenic myocardial proteins from small samples of myocardium a technique was developed for rapidly electroeluting proteins separated on a polyacrylamide gel. This system was validated by electroeluting endothelin receptors from human myocardium.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available