title: Proteomic investigation of whole saliva in Wilson's disease.
abstract: Wilson's disease is a rare inherited disorder of copper metabolism, manifesting hepatic, neurological and psychiatric symptoms. Early diagnosis is often unfeasible and a unique diagnostic test is currently inapplicable. We performed the qualitative/quantitative characterization of the salivary proteome/peptidome of 32 Wilson's disease patients by an integrated top-down/bottom-up approach. Patients exhibited significant higher levels of S100A9 and S100A8 proteoforms, and their oxidized forms with respect to controls. Oxidation occurred on methionine and tryptophan residues, and on the unique cysteine residue, in position 42 in S100A8, and 3 in S100A9, that generated glutathionylated, cysteinylated, sulfinic, sulfonic, and disulfide dimeric forms. Wilson's disease patient saliva showed high levels of two new fragments of the polymeric immunoglobulin receptor, and of α-defensins 2 and 4. Overall, the salivary proteome of Wilson's disease patients reflected oxidative stress and inflammatory conditions characteristic of the pathology, highlighting differences that could be useful clues of disease exacerbation.
authors.affiliation: Department of Life and Environmental Sciences, Biomedical section, University of Cagliari, Monserrato Campus 09042, Monserrato, CA, Italy. Electronic address: tcabras@unica.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cabras
authors.affiliation: Department of Life and Environmental Sciences, Biomedical section, University of Cagliari, Monserrato Campus 09042, Monserrato, CA, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Sanna
authors.affiliation: Department of Life and Environmental Sciences, Biomedical section, University of Cagliari, Monserrato Campus 09042, Monserrato, CA, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Manconi
authors.affiliation: Department of Surgery Sciences, University of Cagliari, Monserrato Campus 09042, Monserrato, CA, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Fanni
authors.affiliation: Department of Medical Sciences "M. Aresu", AOU, University of Cagliari, Monserrato Campus 09042, Monserrato, CA, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Demelia
authors.affiliation: Department of Medical Sciences "M. Aresu", AOU, University of Cagliari, Monserrato Campus 09042, Monserrato, CA, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Sorbello
authors.affiliation: Biochemistry and Clinical Biochemistry Institute, Medicine Faculty, Catholic University of Rome, L.go F. Vito 1, 00168 Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Iavarone
authors.affiliation: Biochemistry and Clinical Biochemistry Institute, Medicine Faculty, Catholic University of Rome, L.go F. Vito 1, 00168 Rome, Italy; Institute of Chemistry of the Molecular Recognition CNR, L.go F. Vito 1, 00168 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Castagnola
authors.affiliation: Department of Surgery Sciences, University of Cagliari, Monserrato Campus 09042, Monserrato, CA, Italy.
authors.forename: Gavino
authors.initials: G
authors.lastname: Faa
authors.affiliation: Department of Life and Environmental Sciences, Biomedical section, University of Cagliari, Monserrato Campus 09042, Monserrato, CA, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Messana
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006527:Hepatolenticular Degeneration / Q000378:metabolism*; D006801:Humans; D008297:Male; D020543:Proteome / Q000737:chemistry* / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: HPLC–ESI-MS; Human saliva; Oxidative stress; Proteomics; S100A8; S100A9; Wilson's disease; pIgR; α-Defensins