Abstract
BackgroundProteasomes 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.MethodsSerum 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.ResultsThe 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).ConclusionThe serum level of 20S-proteasome may be a useful marker for disease activity in AAV.
Highlights
Proteasomes are found in both the cell nucleus and cytoplasm and play a major role in the ubiquitindependent and -independent non-lysosomal pathways of intracellular protein degradation
There was no patients treated with any immunosuppressant in both active and inactive vasculitis, but all inactivevasculitis patients had treated with corticosteroids
There was no relationship between the MPO-antineutrophil cytoplasmic antibody (ANCA) titers and the serum 20S-proteasome levels, these elevations were associated with disease activity
Summary
Proteasomes are found in both the cell nucleus and cytoplasm and play a major role in the ubiquitindependent and -independent non-lysosomal pathways of intracellular protein degradation. Proteasomes are involved in the turnover of various regulatory proteins, antigen processing, cell differentiation, and apoptosis. Proteasomes are located in both the nucleus and cytoplasm of cells, and they play a major role in the ubiquitin-dependent and ubiquitin-independent nonlysosomal pathways of intracellular protein degradation [1, 2]. Three of the seven beta subunits have proteolytic sites; the β1, β2, and β5 subunits are associated with caspase-like, trypsin-like, and chymotrypsin-like activities, respectively [10] These β1, β2, and β5 subunits cleave peptide bonds at post-acidic, −basic, and -hydrophobic amino acid residues, respectively [10]. Subunits β1, β2, and β5 could be replaced with β1i, β2i, and β5i by interferon-gamma (IFNγ), and this IFN-γ-inducible proteasome isotype is called the immunoproteasome [11]
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