What is new in systemic vasculitis?
Authors: C G M KALLENBERG
Journal: Annals of the Rheumatic Diseases (2000)

the 9th International Vasculitis/ ANCA Workshop was held at the University Hospital Groningen, The Netherlands. 1 This series of workshops started as an informal ANCA directed workshop in 1989 in Copenhagen and has grown into an international meeting dealing with the whole spectrum of primary systemic vasculitides, including ANCA associated vasculitis.The present workshop was attended by more than 300 delegates from 19 countries. Endothelium-leucocyte interactionsThe first part of the workshop dealt with endotheliumleucocyte interaction and the role of autoantibodies in this process.Mayet (Mainz, Germany) reviewed the studies of his group showing that endothelial cells, but also other cells like tubular epithelial cells and lung epithelium, express proteinase 3 (PR3), the main target antigen of antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis.Expression was shown not only at the protein level but also at the mRNA level.Stimulation with proinflammatory cytokines resulted in a strong expression of PR3 at the surface of endothelial cells, making PR3 accessible for circulating PR3-ANCA.Indeed, PR3-ANCA were able to upregulate the expression of adhesion molecules and the production of interleukin 8 (IL8) by endothelial cells that were prestimulated with proinflammatory cytokines such as tumour necrosis factor .Daha et al (Leiden, The Netherlands) were not able to confirm PR3 expression by endothelial cells.In contrast, they demonstrated a PR3-binding molecule of 111 kDa on the membrane of endothelial cells.Adding PR3, both in its enzymatically active and inactive form, to endothelial cells resulted in enhanced production of IL8, a strong chemoattractant for neutrophils, and of MCP-1, which is chemotactive for monocytes and T cells.In addition, incubation of endothelial cells with PR3 resulted in upregulation of endothelial leucocyte adhesion molecules.Also, dose dependent apoptosis and cytolysis of endothelial cells was seen in vitro after addition of PR3.Pendergraft and Yang (Chapel Hill, NC, USA) showed, in concordance with the data of Daha, that the proteolytically inactive C terminal part of PR3 can induce apoptosis of endothelial cells and that internalisation of PR3 (and myeloperoxidase (MPO)) results in endothelial damage.Thus PR3 released from neutrophils, may directly activate or damage endothelial cells by interacting with specific (?) receptors.Whether PR3 is expressed by endothelial cells, is still a matter of debate.How do autoantibodies aVect neutrophil-endothelium interaction in systemic vasculitis?Meroni (Milan, Italy) discussed the role of anti-endothelial antibodies.The antigenic targets of those antibodies are, as yet, poorly characterised.Nevertheless, in vitro studies have shown their potential to activate endothelial cells to the production of cytokines and the expression of adhesion molecules and their ability to induce apoptosis of endothelial cells.Savage (Birmingham, UK) presented new evidence to explain why neutrophils are retained within the microvasculature and damage the endothelium in ANCA associated small vessel