Wegener granulomatosis is a systemic disease with a complex genetic background. It is characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract, glomerulonephritis, vasculitis, and the presence of antineutrophil cytoplasmatic autoantibodies (ANCAs) in patient sera.

 These ANCAs are antibodies to a defined target antigen, proteinase-3 (PR3) (MIM.177020), that is present within primary azurophil granules of neutrophils (PMNs) and lysozymes of monocytes.

 On cytokine priming of PMNs, PR3 translocates to the cell surface, where PR3-ANCAs can interact with their antigens and activate PMNs.

 PMNs from patients with active WG express PR3 on their surface, produce respiratory burst, and release proteolytic enzymes after activation with PR3-ANCAs. The consequence is a self-sustaining inflammatory process. (#14968360#)

Localization

 pulmonary Wegener granulomatosis

Predisposition

 locus 6p21.3 (#14968360#)

References

 Yi ES, Colby TV. Wegener's granulomatosis. Semin Diagn Pathol. 2001 Feb;18(1):34-46. PMID: #11296992#