The anti-neutrophil cytoplasm antibody (ANCA) associated vasculitides (AAV) are associated with considerable morbidity and mortality. The main aim of this study was to assess factors affecting outcome for patients with AAV.
Factors affecting outcome for over 500 patients with AAV were assessed. For some patients, this assessment included histological factors. AAV patients with severe renal involvement were also studied. The clinical significance of the B cell survival factors BlyS and APRIL was assessed. In addition, the effect of a BlyS inhibitor was evaluated using the in vivo model of AAV, experimental autoimmune vasculitis (EAV).
Increased age and the requirement for renal replacement therapy (RRT) at presentation were associated with poorer survival. Decade of diagnosis was predictive of outcome which improved with increasing decade. Histological features were assessed for 104 patients and a validation study carried out of the International classification described by Berden et al in 2010. The histological classification was not predictive of renal outcome in our study. One hundred and eighty patients with AAV and an eGFR of <15 ml/min/1.73 m2 were also studied. Fifty nine percent of patients who presented dialysis dependent gained independent renal function at 1 year. Patients with severe renal involvement who presented independent of dialysis had significantly improved outcome.
Serum BlyS levels were found to be raised in patients with active AAV and those in remission, treated with rituximab. APRIL levels were also raised in active patients. The use of a BlyS inhibitor as an induction agent resulted in marked improvement in EAV but treatment of established disease was less effective. An understanding of factors predictive of prognosis in AAV is necessary to balance the risk of immunosuppression with that of the disease process itself and aid the individualisation of therapy for patients. Work described in this thesis has contributed to this understanding