So – what's new?

Welcome to the 14th International Vasculitis and ANCA Workshop in Lund and Copenhagen. Since the first International ANCA Workshop held in Copenhagen in January 1988, a simple PubMed search tells us that 4594 papers have been mentioning ANCA during these 21 years. Less would also qualify for the term ‘impressive’! Since 1988, the diversity of ANCA and its relevance for diagnosis and pathogenesis has sparked off a huge amount of serological, clinical and basic scientific activity. This is reflected in the increasing number of abstracts over the years, now reaching 232 accepted abstracts for the present workshop. It soon became evident that ANCA could be directed against several neutrophil cytoplasmic antigens, with PR3 (see abbreviations section) being the main target for ANCA in WG, and MPO the main target in MPA. With ANCA being present in active and relapsing vasculitis, a pathogenic role of ANCA was suggested and a large body of evidence based on in vitro and animal experiments supports this idea. However, it is still unclear why the presence of large amounts of ANCA in patients off treatment does not lead to relapse and neither which mechanisms ignite this activity. Infections are reported to initiate a relapse – and the role of the nasal carriage of Staphylococcus aureus has been scrutinized – but exactly how this works is unclear. TNF-a, which is generated in response to an infection, has a pivotal role and is necessary for the activation of the inflammatory cells with ANCA. However, anti-TNF-a treatment has not solved the therapeutic problem; so many other players are in the field. A large number of these players are present in granulomas. These could therefore be thought of as small factories producing not only ANCA but also a number of important disease regulating substances being released locally and systemically. Such pathogenic pathways may be important in WG – but what happens in MPA, where there are no granulomas? And even more off the pattern: What happens in PAN and large-vessel vasculitis, where there is no ANCA? Is vasculitis just vasculitis or are there important differences with implications for treatment? So far, our therapeutic endeavors in several RCTs have primarily focused on minimizing the use of CYC, but the therapeutic effect of this alkylating agent is still – like the use of corticosteroids and the other im mune modulating drugs in play – based on general immunosuppression and not a specific action directed against a well-defined pathogenic mechanism. AntiCD20 therapy may do the job – but is not a specific treatment either. T cells and the other immunocompetent cells are also of importance not only for regulation of the immune response but also as effector cells. Gene microarray technology has opened up for looking at the molecular regulation of these disease processes and we can see differences between active WG and active SLE in the activation pattern of the cells, but the interactions of the regulatory mechanisms still evade us. This still hampers a rational and specific therapeutic approach. ANCA is not just observed in primary vasculitic diseases. BPI-ANCA is prevalent in cystic fibrosis with Pseudomonas aeruginosa infections and can – together with HNE-ANCA, Lactoferrin-ANCA and MPOANCA – be detected in IBD and PSC. PR3-ANCA may be found in bacterial endocarditis. ANCAs could therefore be part of a primitive regulatory system of the inflammatory response – perhaps regulated by complementary ANCA? Let us not forget that autoimmunity is an important factor in expelling cancer cells. The treatment of autoimmunity is therefore a potential trade-off for cancer. But what exactly is ANCA? ANCAs appear to be heterogeneous, polyclonal immunoglobulins that, even though they are antigen specific, have several potential functions. ANCA is not just ANCA, but can we identify which functions are important in which situations? Instead of attempts at standardizing ANCA assays – which has been carried out several times – we might be better off focusing on the differences in performance. There is still much unsolved business. This is why we are here. We look forward to having you with us in the quest to find the right answers – and ask the right questions. We are also indebted to our sponsors for making this possible. Your local organizing committee Sweden: Mårten Segelmark, Kerstin Westman, Daina Selga, Gunnar Sturfelt, Ola Nived, Thomas Hellmark, Jörgen Wieslander and Sophie Ohlsson. Denmark: Niels Rasmussen, Wladimir Szpirt, Bo Baslund, Gunnar Houen and Niels Heegaard. APMIS 117 (Suppl. 127): 1 r 2009 The Authors Journal Compilation r 2009 APMIS DOI 10.1111/j.1600-0463.2009.02468.x