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|Title||Diagnostic and prognostic aspects of anti-neutrophil cytoplasmic antibodies in systemic vasculitis|
Department of Nephrology
|Full-text||Available as PDF|
|Defence place||Föreläsningssalen Optimahuset Barngatan2 Universitetssjukhuset i Lund|
|Opponent||Professor M.R. Daha|
|Publisher||Daina Selga Department of Nephrology, Clinical Sciences, Lund Faculty of Medicine Lund, Sweden|
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.
Medicine and Health Sciences
|Keywords||Immunologi, transplantation, serologi, serology, epitope, Wegener's granulomatosis, microscopic polyangiitis, polyarteritis nodosa, capture ELISA, Immunology, anti-neutrophil cytoplasmic antibody, proteinase 3, vasculitis, nephrology, Urologi, nefrologi, Urology|
Kerstin Westman, Daina Selga, Per Bygren, Mårten Segelmark, Bo Baslund, Allan Wiik and Jörgen Wieslander. 1998. Clinical evaluation of a capture ELISA for detection of proteinase-3 antineutrophil cytoplasmic antibody. Kidney International, vol 53 pp 1230-1236. Department of nephrology, Clinical Sciences Lund, Lund University, Sweden
Kerstin Westman, Daina Selga, Per-Erik Isberg, Anna Bladström and Håkan Olsson. 2003. High proteinase 3-anti-neutrophil cytoplasmic antibody (ANCA) level measured by the capture enzyme-linked immunosorbent assay method is associated with decreased patient survival in ANCA-associated vasculitis with renal involvement Journal of American Society of Nephrology, vol 14 pp 2926-2933. Department of Nephrology, Clinical Sciences Lund, Lund University, Sweden
Daina Selga, Aladdin Mohammad, Gunnar Sturfelt and Mårten Segelmark. 2006. Polyarteritis nodosa when applying the Chapel Hill nomenclature - a descriptive study on ten patients Rheumatology, vol 45 pp 1276-1281. Department of Nephrology,Clinical Sciences Lund, Lund University, Sweden
Daina Selga, Mårten Segelmark, Jörgen Wieslander, Lena Gunnarsson and Thomas Hellmark. 2004. Epitope mapping of anti-PR3 antibodies using chimeric human/moue PR3 recombinant proteins Clinical and experimental immunology, vol 135 pp 164-172. Dep of Nephrology, Clinical Sciences Lund, Lund University, Sweden
Daina Selga, Thomas Hellmark, Lena Gunnarsson, Kerstin Westman and Mårten Segelmark. 2007. Capture ELISA for PR3-ANCA is superior to detect and predict relapses of vaculitis compared to direct ELISA based on native PR3, recombinant PR3 or chimeric mouse/human PR3 constructs pp 1-13. Dep of Nephrology, Clinical Sciences Lund, Lund University, Sweden (manuscript)