Reduced Mucin-7 (Muc7) Sialylation and Altered Saliva Rheology in Sjögren's Syndrome Associated Oral Dryness

Abstract

Sjö gren'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 Sjö gren'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. Sjö gren'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 Sjö gren's, particularly on MUC7. LC-MS/MS analysis of O-glycans released from MUC7 by ␤-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. Molecular & Cellular

Variation of Human Salivary O-Glycome

“…The MS/MS fragmentation data of procainamide labelled O-glycans contained diagnostic fragment ions characteristic of core type or blood group epitope consistent with previously reported data [29, 21, 48, 49]. The O-glycans carried the blood group H-epitopes Fucα1-2Galβ1 (diagnostic structure: Fuc-Hex) which is usually modified by a single monosaccharide residue (Galα1-3- or GalNAcα1-3-) and determines ABO blood groups [31, 50, 51].…”

Aging‐related changes in quantity and quality of saliva: Where do we stand in our understanding?

“…Currently oral tribology is emerging as a promising tool to quantify friction and lubrication of food‐saliva mixtures in the oral mucosa using in vitro polymeric set up (Laguna et al, ; Laguna, Farrell, Bryant, Morina, & Sarkar, ; Laguna & Sarkar, ). Studies involving xerostomia patients have reported reduced sulfation of salivary mucins (both MUC1 and MUC2), which may affect the lubricating property of saliva (Chaudhury et al, ). However, there is no tribological work published to date, regarding the change of saliva with age.…”

“…Most of the studies conducted with salivary changes are conducted with patients with burning mouth syndrome (Nagler, 2004), Sjögren's syndrome (Chaudhury, Proctor, Karlsson, Carpenter, & Flowers, 2016), or salivary analysis have been conducted after radiotherapy (Eliasson, Almståhl, Lingström, Wikström, & Carlén, 2005). Interestingly, studies on changes in salivary composition in healthy elderly individuals are relatively scarce.…”

Salivary Interleukin 6 and Sialic acid in Periodontitis

“…This result explores the suggestion of 41 that terminal sialic acid of free glycoprotein mucin is important component of interaction with bacteria protein and prevents colonization by aggregation and swallowing and McBride and Gisslow 42 who showed a correlation between the amounts of sialic acid released from normal saliva and its aggregating activity. Association may due to IL-6 in modulation protein secretion and glycosylation as suggested by previous studies Groux-Degroote et al 43 , and Chaudhury et al 44 that changes in glycosylation of mucin may induce interleukin 6 secretion.…”