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Diagnostic and prognostic aspects of anti-neutrophil cytoplasmic antibodies in systemic vasculitis

Selga, Daina LU (2007)
Abstract
Primary systemic vasculitis is associated with a high mortality if left untreated and it is essential to make the diagnosis before permanent organ damage has occurred. In this thesis the diagnostic and prognostic significance of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic vasculitis is investigated.



The clinical significance of a capture enzyme-linked immunosorbent assay (ELISA) based on the monoclonal antibody 4A3 for detection of antibodies against proteinase 3 (PR3-ANCA) was evaluated and found to have a high sensitivity and specificity. It was shown that patients with high levels of PR3-ANCA as measured by the capture ELISA have a poorer survival and worse renal outcome and are more prone to relapse. In... (More)
Primary systemic vasculitis is associated with a high mortality if left untreated and it is essential to make the diagnosis before permanent organ damage has occurred. In this thesis the diagnostic and prognostic significance of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic vasculitis is investigated.



The clinical significance of a capture enzyme-linked immunosorbent assay (ELISA) based on the monoclonal antibody 4A3 for detection of antibodies against proteinase 3 (PR3-ANCA) was evaluated and found to have a high sensitivity and specificity. It was shown that patients with high levels of PR3-ANCA as measured by the capture ELISA have a poorer survival and worse renal outcome and are more prone to relapse. In comparison the symptoms, signs and clinical course of a cohort of patients with vasculitis but without ANCA, with the diagnosis of polyarteritis nodosa, were described.



Recombinant chimeric molecules were produced in order to map epitopes of monoclonal antibodies to PR3. The clinical utility of these chimeric proteins in the diagnosis and follow-up of patients with PR3-ANCA positive vasculitis was studied and these chimeric molecules were not found to be better than capture ELISA using native PR3. It was observed that samples from the same patient during one exacerbation episode always exhibited a similar pattern of reactivity and that some patients exhibited the same pattern at diagnosis and subsequent flares, while in many patients the pattern changed considerably over time indicating epitope shift during the course of disease. (Less)
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author
supervisor
opponent
  • Professor Daha, M.R., Department of Nephrology, Leiden University Medical Center, The Neteherlands
organization
publishing date
type
Thesis
publication status
published
subject
keywords
transplantation, Immunologi, serologi, serology, epitope, Wegener's granulomatosis, microscopic polyangiitis, polyarteritis nodosa, capture ELISA, Immunology, anti-neutrophil cytoplasmic antibody, proteinase 3, vasculitis, nephrology, Urologi, nefrologi, Urology
pages
63 pages
publisher
Daina Selga Department of Nephrology, Clinical Sciences, Lund Faculty of Medicine Lund, Sweden
defense location
Föreläsningssalen Optimahuset Barngatan2 Universitetssjukhuset i Lund
defense date
2007-05-18 09:00
ISSN
1652-8220
ISBN
978-91-85559-65-7
language
English
LU publication?
yes
id
93a8b5cd-79fd-4ddd-9536-ae1c2eaabccd (old id 548571)
date added to LUP
2007-09-12 09:48:33
date last changed
2016-09-19 08:44:55
@phdthesis{93a8b5cd-79fd-4ddd-9536-ae1c2eaabccd,
  abstract     = {Primary systemic vasculitis is associated with a high mortality if left untreated and it is essential to make the diagnosis before permanent organ damage has occurred. In this thesis the diagnostic and prognostic significance of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic vasculitis is investigated.<br/><br>
<br/><br>
The clinical significance of a capture enzyme-linked immunosorbent assay (ELISA) based on the monoclonal antibody 4A3 for detection of antibodies against proteinase 3 (PR3-ANCA) was evaluated and found to have a high sensitivity and specificity. It was shown that patients with high levels of PR3-ANCA as measured by the capture ELISA have a poorer survival and worse renal outcome and are more prone to relapse. In comparison the symptoms, signs and clinical course of a cohort of patients with vasculitis but without ANCA, with the diagnosis of polyarteritis nodosa, were described.<br/><br>
<br/><br>
Recombinant chimeric molecules were produced in order to map epitopes of monoclonal antibodies to PR3. The clinical utility of these chimeric proteins in the diagnosis and follow-up of patients with PR3-ANCA positive vasculitis was studied and these chimeric molecules were not found to be better than capture ELISA using native PR3. It was observed that samples from the same patient during one exacerbation episode always exhibited a similar pattern of reactivity and that some patients exhibited the same pattern at diagnosis and subsequent flares, while in many patients the pattern changed considerably over time indicating epitope shift during the course of disease.},
  author       = {Selga, Daina},
  isbn         = {978-91-85559-65-7},
  issn         = {1652-8220},
  keyword      = {transplantation,Immunologi,serologi,serology,epitope,Wegener's granulomatosis,microscopic polyangiitis,polyarteritis nodosa,capture ELISA,Immunology,anti-neutrophil cytoplasmic antibody,proteinase 3,vasculitis,nephrology,Urologi,nefrologi,Urology},
  language     = {eng},
  pages        = {63},
  publisher    = {Daina Selga Department of Nephrology, Clinical Sciences, Lund Faculty of Medicine Lund, Sweden},
  school       = {Lund University},
  title        = {Diagnostic and prognostic aspects of anti-neutrophil cytoplasmic antibodies in systemic vasculitis},
  year         = {2007},
}