Serum 20S proteasome levels are associated with disease activity in MPO-ANCA-associated microscopic polyangiitis

Hiroshi Maruyama; Kouichi Hirayama; Marina Yamashita; Kentaro Ohgi; Ryuji Tsujimoto; Mamiko Takayasu; Homare Shimohata; Masaki Kobayashi

doi:10.1186/s41927-020-00137-4

Serum 20S proteasome levels are associated with disease activity in MPO-ANCA-associated microscopic polyangiitis

BMC Rheumatol. 2020 Aug 25:4:36. doi: 10.1186/s41927-020-00137-4. eCollection 2020.

Authors

Hiroshi Maruyama¹, Kouichi Hirayama¹, Marina Yamashita¹, Kentaro Ohgi^{1

2}, Ryuji Tsujimoto^{1

3}, Mamiko Takayasu¹, Homare Shimohata¹, Masaki Kobayashi¹

Affiliations

¹ Department of Nephrology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami, Ibaraki, 300-0395 Japan.
² Department of Intensive Care Medicine, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki, Japan.
³ Department of Nephrology, Tokyo Medical University, Shinjuku, Tokyo, Japan.

Abstract

Background: 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.

Keywords: 20S-proteasome; ANCA-associated vasculitis; Disease activity; Microscopic polyangiitis; Proteasome.