Friederich Wegener’s original paper “On generalised septic vessel disease” suggests he thought it likely there was an infectious cause for the condition which now bears his eponym.1 The characteristic pathological features of Wegener granulomatosis (WG) are: a necrotising granulomatous inflammation of the respiratory tract with vasculitis affecting both arteries and veins; focal necrotising glomerulonephritis; and a varying degree of systemic vasculitis—the so-called “Wegener’s triad”.2 The granulomatous inflammation is conspicuous for the absence of any obvious microorganism, although granulomatous infections can sometimes be misdiagnosed as WG.3 During the 70 years since Wegener’s description there have been some remarkable advances in both the diagnosis and treatment of this condition and in our understanding of its pathogenesis. However, the precise nature of the initiating factor(s) remains elusive.

What we do know is that there is a strong association between WG and the human leucocyte antigen (HLA)-DPB1*0401 allele, suggesting that there is an inherited predisposition for the condition.4 Interestingly, there is also an association with α-1 antitrypsin deficiency.5 We also know that virtually all patients who subsequently develop the systemic disease have circulating antineutrophil cytoplasmic antibodies (ANCAs) and these are mainly directed against proteinase-3 (PR3), the so-called “Wegener’s autoantigen”—a serine protease which regulates cell proliferation, differentiation and death.6 This antibody has proved to be a useful biomarker for the diagnosis of WG,7 8 although less so for the likelihood of relapse.9 Furthermore, our increasing knowledge of its biological properties has provided new insights into the pathogenesis of WG. Specifically, …