- Meeting abstract
Interference of PR3-ANCA with the enzymatic activity of PR3
Arthritis Research & Therapy volume 4, Article number: 80 (2002)
Anti-neutrophil cytoplasmic antibodies (ANCA) against proteinase 3 (PR3) are strongly associated with Wegener's granulomatosis (WG) and are thought to be involved in its pathogenesis. In vitro functional effects of these antibodies have been suggested to correspond better to disease activity than levels of PR3-ANCA.
To investigate the relation between functional effects of PR3-ANCA and disease activity, we tested IgG from sera of 43 WG patients and four controls for their capacity to interfere with the proteolytic activity of PR3. Blood was drawn either during active disease or during remission of WG. The enzymatic activity of PR3 was determined using MeSuc-AAPV-pNA, casein, and by complexation of PR3 with α-1-antitrypsin (α-1-AT).
Most of the IgG samples from WG patients inhibited the enzymatic activity of PR3 and the complexation of PR3 with α-1-AT. A difference in the capacity to interfere with proteolysis of casein and with complexation of PR3 with α-1-AT was observed between samples taken during active disease and during remission of WG, but this was not observed for the hydrolysis of MeSuc-AAPV-pNA. However, PR3-ANCA titers giving fifty percent inhibition of the PR3/α-1-AT complexation and the proteolytic activity of PR3 for the hydrolysis of MeSuc-AAPV-pNA were lower for remission samples compared to samples during active disease, indicating a relatively higher inhibitory activity in the former samples. PR3-ANCA titers correlated with the inhibitory activity both for patients with active disease and for patients during remission.
With a fixed amount of IgG, PR3-ANCA-containing IgG from patients with active disease had a higher inhibitory capacity towards the proteolytic activity of PR3 than did PR3-ANCA-containing IgG from patients during remission of WG. However, when correcting the results for the PR3-ANCA titer, PR3-ANCA of patients during remission had a relatively higher inhibitory capacity towards the proteolytic activity of PR3 than did PR3-ANCA of patients during an active phase. These results may indicate that PR3-ANCA of patients with active disease recognize different epitopes on PR3 than do PR3-ANCA of patients during remission of WG. These findings may have relevance for the pathogenicity of the antibodies.
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Rarok, A., van der Geld, Y., Tool, A. et al. Interference of PR3-ANCA with the enzymatic activity of PR3. Arthritis Res Ther 4, 80 (2002). https://doi.org/10.1186/ar526
- Public Health
- Enzymatic Activity
- Inhibitory Activity
- Proteolytic Activity
- Functional Effect