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Title: Intestinal immunology in man
Author: Humphreys, Kenneth Andrew
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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Loss of IgG to the gut in patients with inflammatory bowel disease (IBD) can arise from plasma or by local production from cells in the lamina propria. The source of IgG in WGLF was shown to be predominantly plasma since the relative coefficient of excretion for IgG in WGLF was similar to albumin for all colonic IBD patients with a range of disease activity. As albumin is much mores susceptible to proteolysis than are immunoglobulins, the study was restricted to patients with colonic disease and without extremes of WGLF protease activity. It has been assumed that protein loss occurs from the site diagnosed as diseased by clinical assessment. To confirm that plasma leakage is the major source of WGLF IgG in patients with colonic IBD, loss of another plasma protein, complement C3, was investigated. A competitive ELISA was developed to measure C3 in WGLF. This requires binding of a single antibody which enables detection of both immune complexes and free C3. WGLF C3 was raised in patients with active IBD. This loss mirrored that of IgG and albumin, showing no diagnostic specificity. In patients with ulcerative colitis, the relative loss of C3 was similar to that of albumin. In contrast, patients with colonic Crohn's disease (CD) show twofold loss of C3 relative to albumin, indicating that mucosal production was a major contributor to WGLF C3. As patients with inactive CD had slightly raised WGLF C3, this may indicate early clinical relapse. The relationship between WGLF C3 and relapse of CD was investigated by follow up of 43 patients for one year after gut lavage. Of 10 who relapsed, 8 had normal WGLF C3 whereas of 15 patients who remained in steroid free remission, 8 had raised WGLF C3. There was a risk factor of 4.4 for relapse in patients with inactive CD who had normal WGLF C3. This might suggest complement deposition or a protective role of complement e.g. clearing apoptotic cells. These hypotheses could be further investigated using intestinal biopsies. This work has been supported in part form a MRC grant to exploit the potential of WGLF.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available