OBJECTIVE: It has been postulated that antineutrophil cytoplasmic antibody (ANCA)-induced degranulation of primed granulocytes and monocytes is involved in the pathogenesis of ANCA-associated vasculitis. Since elastase is the major lysosomal protein released during leukocyte degranulation, we investigated cell activation in vivo in patients with ANCA-associated vasculitis by determining complexed plasma elastase levels. METHODS: Plasma elastase complexed with alpha1-antitrypsin was measured in 20 patients with ANCA-associated vasculitis, using an immunoactivation assay. In parallel, C-reactive protein (CRP) and ANCA levels were determined and clinical disease activity was assessed. RESULTS: Complexed elastase levels were significantly elevated in patients with ANCA-associated vasculitis who had not received immunosuppressive therapy (mean +/- SD 71.5 +/- 22.6 microg/liter), compared with healthy volunteers (12.2 +/- 11.4 microg/liter; P < 0.001). Elastase decreased significantly after 2 weeks (46.5 +/- 26.8 microg/liter; P < 0.01) and further after 8-10 weeks of immunosuppressive treatment (28.1 +/- 13.4 microg/liter; P < 0.02), in correlation with decreasing vasculitis activity. Concomitantly, ANCA titers and CRP levels decreased. CONCLUSION: These data support the theory that, by the release of lysosomal proteinases, leukocyte activation may be involved in the pathogenesis of ANCA-associated vasculitis. In addition, plasma elastase may be used as a marker for disease activity.
OBJECTIVE: It has been postulated that antineutrophil cytoplasmic antibody (ANCA)-induced degranulation of primed granulocytes and monocytes is involved in the pathogenesis of ANCA-associated vasculitis. Since elastase is the major lysosomal protein released during leukocyte degranulation, we investigated cell activation in vivo in patients with ANCA-associated vasculitis by determining complexed plasma elastase levels. METHODS: Plasma elastase complexed with alpha1-antitrypsin was measured in 20 patients with ANCA-associated vasculitis, using an immunoactivation assay. In parallel, C-reactive protein (CRP) and ANCA levels were determined and clinical disease activity was assessed. RESULTS: Complexed elastase levels were significantly elevated in patients with ANCA-associated vasculitis who had not received immunosuppressive therapy (mean +/- SD 71.5 +/- 22.6 microg/liter), compared with healthy volunteers (12.2 +/- 11.4 microg/liter; P < 0.001). Elastase decreased significantly after 2 weeks (46.5 +/- 26.8 microg/liter; P < 0.01) and further after 8-10 weeks of immunosuppressive treatment (28.1 +/- 13.4 microg/liter; P < 0.02), in correlation with decreasing vasculitis activity. Concomitantly, ANCA titers and CRP levels decreased. CONCLUSION: These data support the theory that, by the release of lysosomal proteinases, leukocyte activation may be involved in the pathogenesis of ANCA-associated vasculitis. In addition, plasma elastase may be used as a marker for disease activity.
Authors: Marion Haubitz; David M Good; Alexander Woywodt; Hermann Haller; Harald Rupprecht; Dan Theodorescu; Mohammed Dakna; Joshua J Coon; Harald Mischak Journal: Mol Cell Proteomics Date: 2009-06-28 Impact factor: 5.911
Authors: Samantha P Tull; Anne Bevins; Sahithi Jyothsna Kuravi; Simon C Satchell; Bahjat Al-Ani; Stephen P Young; Lorraine Harper; Julie M Williams; George Ed Rainger; Caroline O S Savage Journal: PLoS One Date: 2012-08-29 Impact factor: 3.240