title: Reduced Mucin-7 (Muc7) Sialylation and Altered Saliva Rheology in Sjögren's Syndrome Associated Oral Dryness.
abstract: Sjögren's syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration and hypofunction of salivary and lacrimal glands. This loss of salivary function leads to oral dryness, impaired swallowing and speech, and increased infection and is associated with other autoimmune diseases and an increased risk of certain cancers. Despite the implications of this prevalent disease, diagnosis currently takes years, partly due to the diversity in patient presentation. Saliva is a complicated biological fluid with major constituents, including heavily glycosylated mucins MUC5B and MUC7, important for its viscoelastic and hydrating and lubricating properties. This study investigated Sjögren's patient's perception of dryness (bother index questionnaires) along with the rheological, protein composition, and glycan analysis of whole mouth saliva and the saliva on the mucosal surface (residual mucosal saliva) to understand the properties that most affect patient wellbeing. Sjögren's patients exhibited a statistically significant reduction in residual mucosal saliva, salivary flow rate, and extensional rheology, spinnbarkeit (stringiness). Although the concentration of mucins MUC5B and MUC7 were similar between patients and controls, a comparison of protein Western blotting and glycan staining identified a reduction in mucin glycosylation in Sjögren's, particularly on MUC7. LC-MS/MS analysis of O-glycans released from MUC7 by β-elimination revealed that although patients had an increase in core 1 sulfation, the even larger reduction in sialylation resulted in a global decline of charged glycans. This was primarily due to the loss of the extended core 2 disialylated structure, with and without fucosylation. A decrease in the extended, fucosylated core 2 disialylated structure on MUC7, residual mucosal wetness, and whole mouth saliva flow rate appeared to have a negative and cumulative effect on the perception of oral dryness. The observed changes in MUC7 glycosylation could be a potential diagnostic tool for saliva quality and taken into consideration for future therapies for this multifactorial syndrome.
authors.affiliation: From the ‡Salivary Unit, Mucosal and Salivary Biology, Dental Institute, King's College London, Guy's Hospital, Floor 17, Tower Wing, London SE1 9RT, UK;
authors.forename: Nayab M A
authors.initials: NM
authors.lastname: Chaudhury
authors.affiliation: From the ‡Salivary Unit, Mucosal and Salivary Biology, Dental Institute, King's College London, Guy's Hospital, Floor 17, Tower Wing, London SE1 9RT, UK;
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Proctor
authors.affiliation: §Department of Medical Biochemistry, Institute of Biomedicine, University of Gothenburg, Medicinaregatan 9A, 405 30, Gothenburg, Sweden niclas.karlsson@medkem.gu.se.
authors.forename: Niclas G
authors.initials: NG
authors.lastname: Karlsson
authors.affiliation: From the ‡Salivary Unit, Mucosal and Salivary Biology, Dental Institute, King's College London, Guy's Hospital, Floor 17, Tower Wing, London SE1 9RT, UK;
authors.forename: Guy H
authors.initials: GH
authors.lastname: Carpenter
authors.affiliation: §Department of Medical Biochemistry, Institute of Biomedicine, University of Gothenburg, Medicinaregatan 9A, 405 30, Gothenburg, Sweden.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Flowers
mesh_terms: D002853:Chromatography, Liquid; D006031:Glycosylation; D006801:Humans; D008875:Middle Aged; D055257:Mucin-5B / Q000378:metabolism; D009077:Mucins / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism*; D012471:Salivary Proteins and Peptides / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000175:diagnosis* / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014987:Xerostomia / Q000378:metabolism*
chemical_list: C524578:MUC5B protein, human; C083238:MUC7 protein, human; D055257:Mucin-5B; D009077:Mucins; D012471:Salivary Proteins and Peptides