Immunological mechanisms in primary sclerosing cholangitis : th erole of the anti-neutrophil cytoplasmic antibody
Immunological mechanisms in primary sclerosing cholangitis : th erole of the anti-neutrophil cytoplasmic antibody
An antineutrophil cytoplasmic antibody (ANCA) has recently been described in PSC. The aim of this thesis was to evaluate the role of this fascinating antibody in PSC. At the same time its role in UC was also evaluated.
ANCA was found to be 65% sensitive and 81% specific for PSC and 42% sensitive and 98% specific for UC. In PSC, ANCA was associated with more extensive involvement of the biliary tree and in UC with longer duration of disease. However there was no correlation with other clinical or treatment parameters, suggesting that this antibody is unlikely to have a role in disease pathogenesis. Patients with PSC+UC had higher ANCA titres and increased levels of the IgG3 isotype of ANCA compared to those with UC-only, suggesting some differences in immune regulation. In contrast to some studies, ANCA was not detected in healthy first-degree relatives of patients with PSC and UC.
Previous reports on the auto-antigen for this ANCA have shown it to be specific to neutrophil polymorphs and their immediate precursors. The results from this thesis suggest that multiple antigens may exist. A minority of patients have antibodies against neutrophil granule constituents. However, in some the auto-antigen is at least partly proteineaceous in nature and may possible complex to DNA, as evidenced by its protease and DNAase sensitivity. A positive immunoblot signal was consistently obtained using nuclear subcellular extracts of neutrophils and confocal laser microscopy showed a fluorescence pattern within some nuclei. However histones are not the antigenic target. Molecular sieving experiments suggested that the antigen is greater than 100kD but Western blotting failed to identify a specific band. This suggests that there may be a specific conformational epitope, possibly a protein-DNA complex, which is rendered non-antigenic by this and other identification procedures.
University of Southampton
1997
Bansi, Devinder Singh
(1997)
Immunological mechanisms in primary sclerosing cholangitis : th erole of the anti-neutrophil cytoplasmic antibody.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
An antineutrophil cytoplasmic antibody (ANCA) has recently been described in PSC. The aim of this thesis was to evaluate the role of this fascinating antibody in PSC. At the same time its role in UC was also evaluated.
ANCA was found to be 65% sensitive and 81% specific for PSC and 42% sensitive and 98% specific for UC. In PSC, ANCA was associated with more extensive involvement of the biliary tree and in UC with longer duration of disease. However there was no correlation with other clinical or treatment parameters, suggesting that this antibody is unlikely to have a role in disease pathogenesis. Patients with PSC+UC had higher ANCA titres and increased levels of the IgG3 isotype of ANCA compared to those with UC-only, suggesting some differences in immune regulation. In contrast to some studies, ANCA was not detected in healthy first-degree relatives of patients with PSC and UC.
Previous reports on the auto-antigen for this ANCA have shown it to be specific to neutrophil polymorphs and their immediate precursors. The results from this thesis suggest that multiple antigens may exist. A minority of patients have antibodies against neutrophil granule constituents. However, in some the auto-antigen is at least partly proteineaceous in nature and may possible complex to DNA, as evidenced by its protease and DNAase sensitivity. A positive immunoblot signal was consistently obtained using nuclear subcellular extracts of neutrophils and confocal laser microscopy showed a fluorescence pattern within some nuclei. However histones are not the antigenic target. Molecular sieving experiments suggested that the antigen is greater than 100kD but Western blotting failed to identify a specific band. This suggests that there may be a specific conformational epitope, possibly a protein-DNA complex, which is rendered non-antigenic by this and other identification procedures.
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Published date: 1997
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Local EPrints ID: 462973
URI: http://eprints.soton.ac.uk/id/eprint/462973
PURE UUID: 1064f634-ecc4-497b-b235-d2a6d899fcaf
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Date deposited: 04 Jul 2022 20:33
Last modified: 04 Jul 2022 20:33
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Author:
Devinder Singh Bansi
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