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Osteoarthritis Cartilage. 2018 Aug;26(8):1078-1086. doi: 10.1016/j.joca.2018.05.017. Epub 2018 May 29.

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

Author information

1
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy. Electronic address: braconi2@unisi.it.
2
Dipartimento Scienze Mediche, Chirurgiche e Neuroscienze, Università degli Studi di Siena, Siena, Italy. Electronic address: giustarini@unisi.it.
3
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy; UOC Patologia Clinica, Azienda Ospedaliera Senese, Siena, Italy. Electronic address: barbara.marzocchi@unisi.it.
4
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy; UOC Medicina Molecolare e Genetica, Azienda Ospedaliera Senese, Siena, Italy. Electronic address: luana.peruzzi@unisi.it.
5
UOC Medicina Molecolare e Genetica, Azienda Ospedaliera Senese, Siena, Italy. Electronic address: m.margollicci@ao-siena.toscana.it.
6
Dipartimento Scienze della Vita, Università degli Studi di Siena, Siena, Italy. Electronic address: ranieri.rossi@unisi.it.
7
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy. Electronic address: bernardini@unisi.it.
8
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy. Electronic address: millucci2@unisi.it.
9
Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK. Electronic address: J.A.Gallagher@liverpool.ac.uk.
10
Hôpital Necker-Enfants Malades, Paris Cedex 15, France. Electronic address: kh.lequansang@aphp.fr.
11
Center for Molecular Medicine, Slovak Academy of Sciences, Bratislava, Slovakia. Electronic address: ueenmri@savba.sk.
12
National Institute of Rheumatic Diseases, Piešťany, Slovakia. Electronic address: rovensky.jozef@gmail.com.
13
Department of Pharmacology, Alkaptonuria Research Office, Faculty of Medicine, Mutah University, Mutah, Karak, Jordan. Electronic address: mohsb74@yahoo.com.
14
Department of Musculoskeletal Biology, University of Liverpool, Liverpool, UK; Department of Clinical Biochemistry and Metabolism, Royal Liverpool University Hospital, Liverpool, UK. Electronic address: lrang@liv.ac.uk.
15
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Siena, Italy. Electronic address: annalisa.santucci@unisi.it.

Abstract

OBJECTIVE:

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).

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

Amyloidosis; Biomarker; Chitotriosidase; Protein thiols; Serum; Serum amyloid A

PMID:
29852277
DOI:
10.1016/j.joca.2018.05.017
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