title: Comparative proteomics in alkaptonuria provides insights into inflammation and oxidative stress.
abstract: Alkaptonuria (AKU) is an ultra-rare inborn error of metabolism associated with a defective catabolism of phenylalanine and tyrosine leading to increased systemic levels of homogentisic acid (HGA). Excess HGA is partly excreted in the urine, partly accumulated within the body and deposited onto connective tissues under the form of an ochronotic pigment, leading to a range of clinical manifestations. No clear genotype/phenotype correlation was found in AKU, and today there is the urgent need to identify biomarkers able to monitor AKU progression and evaluate response to treatment. With this aim, we provided the first proteomic study on serum and plasma samples from alkaptonuric individuals showing pathological SAA, CRP and Advanced Oxidation Protein Products (AOPP) levels. Interesting similarities with proteomic studies on other rheumatic diseases were highlighted together with proteome alterations supporting the existence of oxidative stress and inflammation in AKU. Potential candidate biomarkers to assess disease severity, monitor disease progression and evaluate response to treatment were identified as well.
authors: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, 53100, Siena, Italy.
authors: Daniela
authors: D
authors: Braconi
authors: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, 53100, Siena, Italy.
authors: Giulia
authors: G
authors: Bernardini
authors: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, 53100, Siena, Italy.
authors: Alessandro
authors: A
authors: Paffetti
authors: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, 53100, Siena, Italy.
authors: Lia
authors: L
authors: Millucci
authors: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, 53100, Siena, Italy.
authors: Michela
authors: M
authors: Geminiani
authors: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, 53100, Siena, Italy.
authors: Marcella
authors: M
authors: Laschi
authors: Dipartimento di Scienze Mediche, Chirurgiche e Neuroscienze, Università degli Studi di Siena, 53100, Siena, Italy.
authors: Bruno
authors: B
authors: Frediani
authors: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, 53100, Siena, Italy.
authors: Barbara
authors: B
authors: Marzocchi
authors: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, 53100, Siena, Italy. Electronic address: annalisa.santucci@unisi.it.
authors: Annalisa
authors: A
authors: Santucci
mesh_terms: D062107:Advanced Oxidation Protein Products / Q000097:blood / Q000652:urine; D000368:Aged; D000474:Alkaptonuria / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000652:urine*; D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D020543:Proteome; D040901:Proteomics
chemical_list: D062107:Advanced Oxidation Protein Products; D015415:Biomarkers; D020543:Proteome
keywords: Advanced oxidation protein products; Biomarkers; Osteoarthritis; Plasma; Serum; Serum amyloid a