Proteasomes are found in both the cell nucleus and cytoplasm and play a major role in the
ubiquitin-dependent and -independent non-lysosomal pathways of intracellular protein degradation. Proteasomes are also involved in the turnover of various regulatory
proteins, antigen processing, cell differentiation, and apoptosis. To determine the diagnostic value of serum
proteasome in
antineutrophil cytoplasmic antibody (
ANCA)-associated vasculitis (AAV), we investigated patients with AAV at various stages of the disease.
METHODS: Serum 20S-proteasome was measured by ELISA in 44 patients with MPO-
ANCA-associated
microscopic polyangiitis (MPA) and renal involvement. Thirty of the patients provided serum samples before the initial treatment, and 30 provided samples during remission; 16 provided samples at both time points.
RESULTS: The mean serum 20S-proteasome level was significantly higher in the active-
vasculitis patients (3414.6 ± 2738.9 ng/mL; n = 30) compared to the inactive-
vasculitis patients (366.4 ± 128.4 ng/mL; n = 30; p < 0.0001) and 40 controls (234.9 ± 90.1 ng/mL; p < 0.0001). There were significant positive correlations between the serum 20S-proteasome level and the Birmingham
Vasculitis Activity Score (BVAS) (r = 0.581, p < 0.0001), the
ANCA titer (r = 0.384, p < 0.0001), the white blood cell (WBC) count (r = 0.284, p = 0.0042), the platelet count (r = 0.369, p = 0.0002), and the serum
C-reactive protein (CRP) level (r = 0.550, p < 0.0001). There were significant negative correlations between the serum 20S-proteasome level and both the
hemoglobin concentration (r = - 0.351, p = 0.0003) and the
serum albumin level (r = - 0.460, p < 0.0001). In a multiple regression analysis, there was a significant positive correlation between the serum 20S-proteasome level and only the BVAS results (β = 0.851, p = 0.0009). In a receiver operating curve analysis, the area under the curve for the serum 20S-proteasome level was 0.996, which is higher than those of the WBC count (0.738) and the serum CRP level (0.963).
CONCLUSION: The serum level of 20S-proteasome may be a useful marker for disease activity in AAV.