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Updated: Sep 29, 2026
Monitoring Neutrophil Elastase and Cathepsin G Activity in Human Sputum Samples
Published on: May 21, 2021
Neutrophil membrane expression of proteinase 3 (PR3) is related to relapse in PR3-ANCA-associated vasculitis
Agnieszka A Rarok1, Coen A Stegeman, Pieter C Limburg
1Department of Internal Medicine, University Hospital Groningen, The Netherlands. a.a.rarok@med.rug.nl
Abstract:
Wegener granulomatosis (WG) is strongly associated with the presence of antineutrophil cytoplasm autoantibodies (ANCA) with specificity for proteinase 3 (PR3). Relapses of WG are frequently preceded by a rise of autoantibody titer and PR3-ANCA are able to activate primed neutrophils in vitro. Except being stored intracellularly and translocated to the cell surface upon neutrophil stimulation, PR3 can also be detected on the surface of non-stimulated neutrophils (membrane PR3 or mPR3), with an interindividual variability in percentages of mPR3(-)-positive cells and level of mPR3 expression. This study began with the hypothesis that the presence of PR3 on the surface of non-stimulated neutrophils enables interaction with PR3-ANCA and influences clinical manifestations of the disease. It analyzed mPR3 expression on neutrophils of 89 WG patients in complete remission and 72 healthy controls to evaluate whether the presence of PR3 on the surface of resting neutrophils is related to clinical manifestations of WG and/or to the susceptibility to develop relapses. The number of patients with a bimodal mPR3 expression on resting neutrophils did not differ between patients and controls. However, in WG patients, an increased percentage of mPR3(+) neutrophils and an elevated level of mPR3 expression compared with healthy individuals (P = 0.037) were found. Within the group of WG patients, an elevated level of mPR3 expression was significantly associated with an increased risk for relapse (P = 0.021) and with an increased relapse rate (P = 0.011), but not with the disease extent or particular manifestations at diagnosis or at relapse. These data support the hypothesis that PR3 expression on the membrane of neutrophils plays a role in the pathophysiology of PR3-ANCA associated vasculitis.
Insights
Elevated levels of membrane proteinase 3 (mPR3) on neutrophils are linked to increased relapse risk in Wegener granulomatosis (WG) patients with proteinase 3 antineutrophil cytoplasm autoantibodies (PR3-ANCA). This finding suggests mPR3 plays a role in PR3-ANCA vasculitis.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Wegener granulomatosis (WG), now known as granulomatosis with polyangiitis, is strongly associated with antineutrophil cytoplasm autoantibodies (ANCA) targeting proteinase 3 (PR3).
- Relapses in WG are often preceded by rising autoantibody titers, and PR3-ANCA can activate neutrophils.
- Proteinase 3 (PR3) is found intracellularly but also on the surface of non-stimulated neutrophils (membrane PR3 or mPR3), with variable expression.
Purpose of the Study:
- To investigate the hypothesis that surface-expressed PR3 on non-stimulated neutrophils interacts with PR3-ANCA, influencing WG clinical manifestations.
- To evaluate the relationship between mPR3 expression on resting neutrophils and WG clinical features, including relapse susceptibility.
Main Methods:
- Analysis of mPR3 expression on neutrophils from 89 WG patients in remission and 72 healthy controls.
- Comparison of mPR3 expression levels and percentages between WG patients and controls.
- Correlation analysis between mPR3 expression and WG disease extent, manifestations, relapse risk, and relapse rate.
Main Results:
- No difference in bimodal mPR3 expression was observed between WG patients and controls.
- WG patients exhibited a higher percentage of mPR3(+) neutrophils and elevated mPR3 expression levels compared to healthy individuals (P = 0.037).
- In WG patients, elevated mPR3 expression was significantly associated with increased relapse risk (P = 0.021) and relapse rate (P = 0.011), but not disease extent or specific manifestations.
Conclusions:
- The study supports the hypothesis that membrane-bound PR3 on neutrophils contributes to the pathophysiology of PR3-ANCA-associated vasculitis.
- Elevated mPR3 expression is a potential biomarker for increased relapse risk in WG patients.
- Further research into the role of mPR3 in neutrophil activation and vasculitis pathogenesis is warranted.
