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

Braconi, Daniela; Giustarini, Daniela; Marzocchi, Barbara; Peruzzi, Luana; Margollicci, Maria; Rossi, Ranieri; Bernardini, Giulia; Millucci, Lia; Gallagher, James A.; Sang, Kim Hanh Le Quan; Imrich, Richard; Rovenský, Jozef; Alsbou, Mohammed; Ranganath, L.R.; Santucci, Annalisa

doi:10.1016/j.joca.2018.05.017

Cited by 19 publications

(44 citation statements)

References 86 publications

(88 reference statements)

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“…In Braconi et al . (33), it was also found to be related with AKU severity. As a matter of fact, PTI was found to be directly correlated (Pearson correlation coefficient: 0.332, P = 0.037) with the Health Assessment Questionnaire Disability Index, which is one of the most widely used comprehensive, validated, and patient‐oriented outcome assessment instruments, especially in assessing the level of functional disability for a patient with rheumatoid arthritis (44).…”

Section: Resultsmentioning

confidence: 87%

“…Reactions were completed throught the addition of 1.4 ml of 0.2 M glycine buffer (pH 10.8). Fluorescence of 4‐methylumbelliferone was read in a fluorimeter (excitation 365 nm, emission 435 nm; PerkinElmer, Waltham, MA, USA) (33).…”

Section: Methodsmentioning

confidence: 99%

“…Plates were read on a VersaMax Microplate Reader (Molecular Devices, Sunnyvale, CA, USA) using Ascent software (Thermo Fisher Scientific, Waltham, MA, USA). Quantification of analytes was obtained against polynomial standard curves generated with appropriate standards (33). In all, 96.6% of SAA values are .5 mg/L (33).…”

Section: Saamentioning

confidence: 99%

“…Quantification of analytes was obtained against polynomial standard curves generated with appropriate standards (33). In all, 96.6% of SAA values are .5 mg/L (33).…”

Section: Saamentioning

confidence: 99%

“…Chitotriosidase is an inflammatory protein secreted by activated macrophages. Its activity was determined according to work of (33).…”

Section: Chitotriosidasementioning

confidence: 99%

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Interactive alkaptonuria database: investigating clinical data to improve patient care in a rare disease

Cicaloni

Spiga

Dimitri³

et al. 2019

The FASEB Journal

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Alkaptonuria (AKU) is an ultrarare autosomal recessive disorder (MIM 203500) that is caused byby a complex set of mutations in homogentisate 1,2‐dioxygenasegene and consequent accumulation of homogentisic acid (HGA), causing a significant protein oxidation. A secondary form of amyloidosis was identified in AKU and related to high circulating serum amyloid A (SAA) levels, which are linked with inflammation and oxidative stress and might contribute to disease progression and patients' poor quality of life. Recently, we reported that inflammatory markers (SAA and chitotriosidase) and oxidative stress markers (protein thiolation index) might be disease activity markers in AKU. Thanks to an international network, we collected genotypic, phenotypic, and clinical data from more than 200 patients with AKU. These data are currently stored in our AKU database, named ApreciseKUre. In this work, we developed an algorithm able to make predictions about the oxidative status trend of each patient with AKU based on 55 predictors, namely circulating HGA, body mass index, total cholesterol, SAA, and chitotriosidase. Our general aim is to integrate the data of apparently heterogeneous patients with AKUAKU by using specific bioinformatics tools, in order to identify pivotal mechanisms involved in AKU for a preventive, predictive, and personalized medicine approach to AKU.—Cicaloni, V., Spiga, O., Dimitri, G. M., Maiocchi, R., Millucci, L., Giustarini, D., Bernardini, G., Bernini, A., Marzocchi, B., Braconi, D., Santucci, A. Interactive alkaptonuria database: investigating clinical data to improve patient care in a rare disease. FASEB J. 33, 12696–12703 (2019). http://www.fasebj.org

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Section: Resultsmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Saamentioning

confidence: 99%

“…Quantification of analytes was obtained against polynomial standard curves generated with appropriate standards (33). In all, 96.6% of SAA values are .5 mg/L (33).…”

Section: Saamentioning

confidence: 99%

“…Chitotriosidase is an inflammatory protein secreted by activated macrophages. Its activity was determined according to work of (33).…”

Section: Chitotriosidasementioning

confidence: 99%

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Interactive alkaptonuria database: investigating clinical data to improve patient care in a rare disease

Cicaloni

Spiga

Dimitri³

et al. 2019

The FASEB Journal

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Increased prevalence of Parkinson's disease in alkaptonuria

et al. 2023

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Amongst a cohort of 88 alkaptonuria (AKU) patients attending the United Kingdom National Alkaptonuria Centre (NAC), four unrelated patients had co‐existing Parkinson's disease (PD). Two of the NAC patients developed PD before receiving nitisinone (NIT) while the other two developed overt PD during NIT therapy. NIT lowers redox‐active homogentisic acid (HGA) and profoundly increases tyrosine (TYR). A further unpublished case of a Dutch patient with AKU and PD on deep brain stimulation is included in this report. A Pubmed search revealed a further five AKU patients with PD, all without NIT usage. The prevalence of PD in AKU in the NAC appears to be nearly 20‐times higher than in the non‐AKU population (p < 0.001) even when adjusted for age. We propose that life‐long exposure to redox‐active HGA may account for the higher prevalence of PD in AKU. Furthermore, the appearance of PD in AKU patients during NIT therapy may be due to unmasking dopamine deficiency in susceptible individuals, as a result of the tyrosinaemia during NIT therapy inhibiting the rate‐limiting brain tyrosine hydroxylase.

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Alkaptonuria – Past, present and future

Davison¹,

Norman²

2023

Advances in Clinical Chemistry

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

Abstract: 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.

Cited by 19 publications

References 86 publications

Interactive alkaptonuria database: investigating clinical data to improve patient care in a rare disease

Interactive alkaptonuria database: investigating clinical data to improve patient care in a rare disease

Increased prevalence of Parkinson's disease in alkaptonuria

Alkaptonuria – Past, present and future

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