Autoimmunity in glomerulonephritis; serological diagnosis and clinical outcome with special reference to Wegener´s granulomatosis and microscopic polyangiitis
Sammanfattning: Autoantibodies of different specificites have been described in association with glomerulonephritis and therefore the aim of this thesis was to improve our knowledge of the different manifestations of autoimmune phenomena which are involved in the glomerulonephritides. Special reference is made to Wegener´s granulomatosis (WG) and microscopic polyangiitis (MP) which are frequently associated with the prevalence of anti-neutrophil cytoplasmic antibodies (ANCA). The present studies revealed that women with glomerulonephritis had a higher prevalence of thyroid peroxidase antibodies (TPO-Ab) which persisted during a three-year follow-up period, in spite of continued immunosuppression. It was also shown that thyroid antibodies were detectable not only in membranous nephropathy, but also in other types of glomerulonephritis. Thyroid disease was documented in 15/122 (12%) in patients with WG or MP. As early diagnosis and treatment are important for the outcome of patients in the rapidly progressive forms of glomerulonephritis, a clinical evaluation of the serological diagnosis was performed. A highly sensitive and specific rapid screening ELISA for anti-glomerular basement membrane antibodies (anti-GBM), Proteinase 3-(PR3-) and Myeloperoxidase- (MPO-)ANCA was developed. A new capture ELISA for the detection of PR3-ANCA was evaluated and found to have a high sensitivity. A retrospective study on patients with WG or MP with renal involvement is presented, revealing that half of the patients relapse and that renal and patient survival in a five-year follow-up is about 70%. Factors important for relapse, renal and patient survival were identified. Notably, the level of PR3-ANCA titre as measured by the capture ELISA was important for the renal outcome. As the immunosuppressive therapy in current use, is described as increasing the risk of cancer, incidence data on cancer were obtained from the population based South Swedish Regional Tumor Registry and are presented here. By an increased attention to these vasculitic disorders and the availability of quickly performed and reliable serological testing there should be a realistic chance to establish an earlier diagnosis and thereby avoiding extensive organ involvement and thus improving the clinical outcome.
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