Cellular immune responses and pathogenesis in c-ANCA positive vasculitides

Very little is known about the cellular immune response in c-ANCA (classical anti-neutrophil cytoplasm antibodies) positive vasculitides or Wegener's granulomatosis (WG). The present review is mainly based on published and unpublished observations of the Cattegat Study Group of Wegener's Granulomatosis. Immunohistochemical examinations of nasal biopsies from untreated patients with active WG revealed the presence of substantial amounts of cells belonging to the immune system (CD3+, CD4+, CD8+, CD20+, CD38+ and CD68+). The IgG response of peripheral mononuclear cells from untreated WG patients to PWM and EBV stimulation was significantly depressed when examined by the reverse haemolytic plaque forming cell assay. T lymphocyte proliferation was observed by in-vitro stimulation with extract of human neutrophil alpha granules, containing the autoantigen for c-ANCA, proteinase-3, only in patients with c-ANCA and active disease. Electron microscopy of biopsies from nasal lesions in untreated patients with active WG did not show structural abnormalities of the organelles of macrophages, giant cells or epithelioid cells. It is concluded that the immune response leading to c-ANCA production involves the full spectrum of immunocompetent cells normally engaged in IgG production to a foreign antigen. This would be in agreement with a theory of cross reactivity of proteinase-3 with a microbial antigen as a pathogenetic mechanism.