Inflammatory and oxidative stress biomarkers in alkaptonuria: data from the DevelopAKUre project


Braconi, D, Giustarini, D, Marzocchi, B, Peruzzi, L, Margollicci, M, Rossi, R, Bernardini, G, Millucci, L, Gallagher, JA ORCID: 0000-0002-0852-279X, Sang, K-H Le Quan et al (show 5 more authors) (2018) Inflammatory and oxidative stress biomarkers in alkaptonuria: data from the DevelopAKUre project. OSTEOARTHRITIS AND CARTILAGE, 26 (8). pp. 1078-1086.

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Abstract

<h4>Objective</h4>The aim of this work was to assess baseline serum levels of established biomarkers related to inflammation and oxidative stress in samples from alkaptonuric subjects enrolled in SONIA1 (n = 40) and SONIA2 (n = 138) clinical trials (DevelopAKUre project).<h4>Methods</h4>Baseline serum levels of Serum Amyloid A (SAA), IL-6, IL-1β, TNFα, CRP, cathepsin D (CATD), IL-1ra, and MMP-3 were determined through commercial ELISA assays. Chitotriosidase activity was assessed through a fluorimetric method. Advanced Oxidation Protein Products (AOPP) were determined by spectrophotometry. Thiols, S-thiolated proteins and Protein Thiolation Index (PTI) were determined by spectrophotometry and HPLC. Patients' quality of life was assessed through validated questionnaires.<h4>Results</h4>We found that SAA serum levels were significantly increased compared to reference threshold in 57.5% and 86% of SONIA1 and SONIA2 samples, respectively. Similarly, chitotriosidase activity was above the reference threshold in half of SONIA2 samples, whereas CRP levels were increased only in a minority of samples. CATD, IL-1β, IL-6, TNFα, MMP-3, AOPP, thiols, S-thiolated protein and PTI showed no statistically significant differences from control population. We provided evidence that alkaptonuric patients presenting with significantly higher SAA, chitotriosidase activity and PTI reported more often a decreased quality of life. This suggests that worsening of symptoms in alkaptonuria (AKU) is paralleled by increased inflammation and oxidative stress, which might play a role in disease progression.<h4>Conclusions</h4>Monitoring of SAA may be suggested in AKU to evaluate inflammation. Though further evidence is needed, SAA, chitotriosidase activity and PTI might be proposed as disease activity markers in AKU.

Item Type: Article
Uncontrolled Keywords: Amyloidosis, Biomarker, Chitotriosidase, Protein thiols, Serum, Serum amyloid A
Depositing User: Symplectic Admin
Date Deposited: 14 Mar 2019 11:15
Last Modified: 07 Feb 2024 15:18
DOI: 10.1016/j.joca.2018.05.017
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3031275
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