Clinical and molecular studies in ANCA associated vasculitis

摘要: ANCA associated vasculitis (AAV) is a heterogeneous group of diseases characterised by sterile pauci-immune systemic small vessel inflammation and closely with the presence anti-neutrophil cytoplasmatic antibodies (ANCA). Although AAV can affect any organ, kidney, skin, lungs upper lower airways are most commonly involved. In some patients there granuloma formation in asthma eosinophilia, based on this be further classified as microscopic polyangiitis (MPA) (no granuloma), granulomatosis (GPA) or eosinophil (EGPA). Induction treatment consists cytotoxic agent combination glucocorticoids usually effective, although relapse, infections drug toxicity remain problem. The aim thesis was to investigate role novel proinflammatory molecules pathogenesis markers disease. We also wanted outcome new therapies. paper I we investigated pro-inflammatory mediator high-mobility box-1 protein (HMGB1) active remission. Elevated levels circulating HMGB1 were found disease compared inactive increased expression renal tissue AAV, indicating for AAV. II carried out long time follow-up treated rituximab second line refractory relapsing that high proportion achieved remission but several adverse events including two cases hepatitis B reactivation. Patients negative conventional positive capture seemed at risk relapse after treatment. III macrophage inhibitory factor thyroid hormones prospectively 30 MIF elevated correlated activity. There hormone alterations triiodothyronine disease, similar what has previously been described critically ill patients. addition an indication interaction between thyroxine sepsis. IV pentraxin – 3 (PTX3) soluable Tumor necrosis factor-like weak inducer apoptosis (sTWEAK) 40 PTX3 severity. sTWEAK did not significantly change remission, vary phenotype. low less likely achieve conclusion may implicated exacerbation possible targets therapy. seems useful marker Rituximab it important assess status concern. LIST OF SCIENTIFIC PAPERS This following papers, which will referred text their Roman numerals. I. Bruchfeld A, Wendt M, Bratt J, Qureshi AR, Chavan S, Tracey KJ, Palmblad K Gunnarsson ”High-mobility antineutrophilic antibody (ANCA)-associated manifestations” Mol Med. 2011 17: 29-35. II. I, J A.”Rituximab ANCA-associated vasculitis: case series 16 patients” Scand Rheumatol. 2012 41:116-9. III. Borjesson O, Avik Anderstam B, Miller EJ, A. ”Macrophage Migration Inhibitory Factor (MIF) Thyroid Hormone Alterations Antineutrophil Cytoplasmatic Antibody (ANCA)-Associated Vasculitis (AAV)” 2013 20:109-14. IV. M Wendt, O Borjesson, A Avik, Bratt, AR Qureshi, Bruchfeld. soluble TWEAK undergoing correlation activity relapse” Manuscript CONTENTS