title: Alterations in the Salivary Proteome and N-Glycome of Sjögren's Syndrome Patients.
abstract: We used isobaric mass tagging (iTRAQ) and lectin affinity capture mass spectrometry (MS)-based workflows for global analyses of parotid saliva (PS) and whole saliva (WS) samples obtained from patients diagnosed with primary Sjögren's Syndrome (pSS) who were enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) as compared with two control groups. The iTRAQ analyses revealed up- and down-regulation of numerous proteins that could be involved in the disease process (e.g., histones) or attempts to mitigate the ensuing damage (e.g., bactericidal/permeability increasing fold containing family (BPIF) members). An immunoblot approach applied to independent sample sets confirmed the pSS associated up-regulation of β2-microglobulin (in PS) and down-regulation of carbonic anhydrase VI (in WS) and BPIFB2 (in PS). Beyond the proteome, we profiled the N-glycosites of pSS and control samples. They were enriched for glycopeptides using lectins Aleuria aurantia and wheat germ agglutinin, which recognize fucose and sialic acid/N-acetyl glucosamine, respectively. MS analyses showed that pSS is associated with increased N-glycosylation of numerous salivary glycoproteins in PS and WS. The observed alterations of the salivary proteome and N-glycome could be used as pSS biomarkers enabling easier and earlier detection of this syndrome while lending potential new insights into the disease process.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.|Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Steven C
authors.identifier: 0000-0002-5366-8931
authors.initials: SC
authors.lastname: Hall
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.|Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Hassis
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.|Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Williams
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.|Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Albertolle
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Akraporn
authors.initials: A
authors.lastname: Prakobphol
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.|Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Dykstra
authors.affiliation: Library and Center for Knowledge Management, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Megan
authors.initials: M
authors.lastname: Laurance
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Katherine
authors.initials: K
authors.lastname: Ona
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.|Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Niles
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.|Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Namrata
authors.initials: N
authors.lastname: Prasad
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gormley
authors.affiliation: Department of Orofacial Sciences, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Caroline
authors.initials: C
authors.lastname: Shiboski
authors.affiliation: Department of Orofacial Sciences, University of California, San Francisco , San Francisco, California 94143, United States.|Russel/Engleman Rheumatology Research Center, Department of Medicine, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Criswell
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.|Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: H Ewa
authors.initials: HE
authors.lastname: Witkowska
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco , San Francisco, California 94143, United States.|Sandler-Moore Mass Spectrometry Core Facility, University of California, San Francisco , San Francisco, California 94143, United States.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Fisher
mesh_terms: D002256:Carbonic Anhydrases / Q000096:biosynthesis; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D037102:Lectins / Q000737:chemistry; D008297:Male; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D010306:Parotid Gland / Q000737:chemistry / Q000378:metabolism; D020543:Proteome / Q000235:genetics*; D012463:Saliva / Q000737:chemistry / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D006023:Glycoproteins; D037102:Lectins; D020543:Proteome; D002256:Carbonic Anhydrases; C477051:carbonic anhydrase VI; D019158:N-Acetylneuraminic Acid
keywords: N-glycosylation; Sjögren’s Syndrome; glycosite; iTRAQ; isobaric mass tagging; lectin affinity capture; parotid saliva; whole saliva