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