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

Abstract

Background: 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 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 20Sproteasome 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.

Functional and quantitative evaluation of the 20S proteasome in serum and intracellular in145 moroccan patients with hematologic malignancies

“…All treated patients showed a significant regression of the serum proteasome level. In fact, the values obtained within the population of MM patients are similar to those published by Jakob et al 2007 [ 17 , 21 ] concluding that the level of circulating proteasome is correlated at the stage of the disease and that the effectiveness of the chemotherapy.…”

Meta-analysis of senescent cell secretomes to identify common and specific features of the different senescent phenotypes: a tool for developing new senotherapeutics

“…Notably, we also detected the presence of 20S proteasome subunits as components of SASP. The 20S proteasome is found in over 25 different body fluids and has been associated with the activity of certain diseases [ 6 , 31 ]. However, the specific function of these proteasome subunits in SASP remains unclear.…”

Vasculitis asociadas a ANCA: análisis de 26 pacientes

“…En este último año, luego de un importante trabajo de colaboración entre la American College of Rheumatology y la European Alliance of Associations for Rheumatology, han surgido los nuevos criterios clasificatorios para las vasculitis asociadas a ANCA 29,[50][51][52] . Se siguen estudiando biomarcadores con el objetivo de encontrar moléculas marcadoras genéricas de inflamación o títulos de ANCA que puedan reflejar fuertemente la actividad de la enfermedad o predecir futuros brotes en vasculitis asociadas a ANCA, lo que sigue siendo difícil de alcanzar [53][54][55][56][57][58][59][60][61][62][63] . Entre ellos, algunos prometedores son los niveles séricos de proteosoma 20S, el CD163 soluble en orina, el suPAR, pentraxina-3 y algunos más tradicionales que están mostrando alguna utilidad, como el índice de masa corporal y el ratio eritrosedimentación/PCR, entre otros [55][56][57][58][59][60][61][62][63] .…”

“…Se siguen estudiando biomarcadores con el objetivo de encontrar moléculas marcadoras genéricas de inflamación o títulos de ANCA que puedan reflejar fuertemente la actividad de la enfermedad o predecir futuros brotes en vasculitis asociadas a ANCA, lo que sigue siendo difícil de alcanzar [53][54][55][56][57][58][59][60][61][62][63] . Entre ellos, algunos prometedores son los niveles séricos de proteosoma 20S, el CD163 soluble en orina, el suPAR, pentraxina-3 y algunos más tradicionales que están mostrando alguna utilidad, como el índice de masa corporal y el ratio eritrosedimentación/PCR, entre otros [55][56][57][58][59][60][61][62][63] . Desde la introducción de la ciclofosfamida y las altas dosis de corticoides, las vasculitis asociadas a ANCA se han transformado de una enfermedad que de 90% de mortalidad al año pasó a ser una enfermedad crónica con remisiones y recaídas 29,[64][65][66] .…”