Complexed plasma elastase as an in vivo marker for leukocyte activation in antineutrophil cytoplasmic antibody-associated vasculitis.
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.


CONCLUSIONS
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.
Haubitz
M
M
Medical School Hannover, Germany.
Schulzeck
P
P
Schellong
S
S
Schulze
M
M
Koch
K M
KM
Brunkhorst
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D006098:Granulocytes / Q000276:immunology*; D014890:Granulomatosis with Polyangiitis / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D019272:Leukocyte Elastase; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000378:metabolism*; D011239:Prednisolone / Q000627:therapeutic use; D012008:Recurrence; D014657:Vasculitis / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D007166:Immunosuppressive Agents; D000515:alpha 1-Antitrypsin; C037741:alpha 1-antitrypsin-leukocyte elastase complex; D003520:Cyclophosphamide; D002097:C-Reactive Protein; D011239:Prednisolone; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D008775:Methylprednisolone