autoimmunity – key to new

ent Updatecating that reduced FcgRIIIb expression could favour neu-trophil activation. Furthermore, Ring finger protein 1 (RING1), retinoid X receptor b (RXRB), PTPN22*620W and HLA-DPB1*0401 alleles all are associated strongly with WG [4,5]. Polymorphism of the gene that encodes inhibitory intracellular protein tyrosine phosphatase non-receptor 22 results in lowered thresholds for T- and B-cell signalling and is associated with several autoimmune dis-eases. By contrast, the role ofHLA-DPB1*0401,RING1 and RXRB polymorphism has not been elucidated in WG so far [3–5]. In chronic beryllium disease – a granulomatous dis-ease caused by occupational beryllium exposure – alleles of human leukocyte antigen-DP (HLA-DP) containing gluta-micacid at position 69 of theb-chain represent a genetic risk factor favouringTh1-responses [6]. The interleukin (IL)-10.2 protease-activated receptor 2 and evokes an exaggerated Th1-type response in WG [12]. Thus, PR3 (and possibly also MPO) displays features of an endogenous ‘danger signal’, inducing autoinflammation reminiscent of MSU-mediated or nucleic-acid-mediated activation of innate immunity. Genetic risk factors favouring inflammation and further endogenous and/or exogenous determinants (e.g. Staphylococcus aureus colonization of the respirat-ory epithelial interface in WG) could link autoinflamma-tion, granuloma formation preferentially affecting the respiratory tract (in WG and CSS but not in MPA) and autoimmunity, giving rise to MPO- and PR3-ANCA formation and ANCA-vasculitis in AAV. Dissecting the mechanisms of autoinflammation will help to identify molecular targets for future therapies aimed at modulat-Letters Antineutrophil cytoplasmic vasculitis: autoinflammati