血清20S蛋白酶体水平与髓过氧化物酶-抗中性粒细胞胞浆抗体相关性显微镜下多血管炎的疾病活动相关。
Serum 20S proteasome levels are associated with disease activity in MPO-ANCA-associated microscopic polyangiitis.
作者信息
Maruyama Hiroshi, Hirayama Kouichi, Yamashita Marina, Ohgi Kentaro, Tsujimoto Ryuji, Takayasu Mamiko, Shimohata Homare, Kobayashi Masaki
机构信息
Department of Nephrology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami, Ibaraki, 300-0395 Japan.
Department of Intensive Care Medicine, Tokyo Medical University Ibaraki Medical Center, Ami, Ibaraki, Japan.
出版信息
BMC Rheumatol. 2020 Aug 25;4:36. doi: 10.1186/s41927-020-00137-4. eCollection 2020.
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; = 30) compared to the inactive-vasculitis patients (366.4 ± 128.4 ng/mL; = 30; < 0.0001) and 40 controls (234.9 ± 90.1 ng/mL; < 0.0001). There were significant positive correlations between the serum 20S-proteasome level and the Birmingham Vasculitis Activity Score (BVAS) ( = 0.581, < 0.0001), the ANCA titer ( = 0.384, < 0.0001), the white blood cell (WBC) count ( = 0.284, = 0.0042), the platelet count ( = 0.369, = 0.0002), and the serum C-reactive protein (CRP) level ( = 0.550, < 0.0001). There were significant negative correlations between the serum 20S-proteasome level and both the hemoglobin concentration ( = - 0.351, = 0.0003) and the serum albumin level ( = - 0.460, < 0.0001). In a multiple regression analysis, there was a significant positive correlation between the serum 20S-proteasome level and only the BVAS results ( = 0.851, = 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.
背景
蛋白酶体存在于细胞核和细胞质中，在细胞内蛋白质降解的泛素依赖性和非依赖性非溶酶体途径中起主要作用。蛋白酶体还参与各种调节蛋白的周转、抗原加工、细胞分化和细胞凋亡。为了确定血清蛋白酶体在抗中性粒细胞胞浆抗体（ANCA）相关血管炎（AAV）中的诊断价值，我们对处于疾病不同阶段的AAV患者进行了研究。
方法
采用酶联免疫吸附测定法（ELISA）检测44例伴有肾脏受累的髓过氧化物酶抗中性粒细胞胞浆抗体（MPO-ANCA）相关显微镜下多血管炎（MPA）患者的血清20S蛋白酶体水平。其中30例患者在初始治疗前提供了血清样本，30例患者在缓解期提供了样本；16例患者在两个时间点均提供了样本。
结果
与非活动性血管炎患者（366.4±128.4 ng/mL；n = 30；P < 0.0001）和40名对照者（234.9±90.1 ng/mL；P < 0.0001）相比，活动性血管炎患者（3414.6±2738.9 ng/mL；n = 30）的血清20S蛋白酶体平均水平显著更高。血清20S蛋白酶体水平与伯明翰血管炎活动评分（BVAS）（r = 0.581，P < 0.0001）、ANCA滴度（r = 0.384，P < 0.0001）、白细胞（WBC）计数（r = 0.284，P = 0.0042）、血小板计数（r = 0.369，P = 0.0002）以及血清C反应蛋白（CRP）水平（r = 0.550，P < 0.0001）之间存在显著正相关。血清20S蛋白酶体水平与血红蛋白浓度（r = -0.351，P = 0.0003）和血清白蛋白水平（r = -0.460，P < 0.0001）之间存在显著负相关。在多元回归分析中，血清20S蛋白酶体水平仅与BVAS结果存在显著正相关（r = 0.851，P = 0.0009）。在受试者工作特征曲线分析中，血清20S蛋白酶体水平的曲线下面积为0.996，高于白细胞计数（0.738）和血清CRP水平（0.963）。
结论
20S蛋白酶体的血清水平可能是AAV疾病活动的一个有用标志物。
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