br Funding Source This study was funded by Mesoblast Inc

Funding Source This study was funded by Mesoblast, Inc.
Contributors
Declaration of Interests
Prior Presentation
Acknowledgements
Introduction In 1933, Henrik Sjögren, in his doctoral dissertation introduced the neologism, keratoconjunctivitis Sicca (Murube, 2010, Sjögren, 1933). His findings now known as Sjögren\'s syndrome (SS), has come to be understood as a multi-faceted autoimmune disorder primarily affecting the salivary and lacrimal glands, presenting with oral and ocular dryness, and often accompanied by extraglandular manifestations. Lymphocytic infiltration of the salivary glands has been a hallmark finding. However, the dysregulated immune response and salivary gland dysfunction are not always correlated and salivary gland dysfunction could precede autoimmunity or even be a result of an independent process in the pathogenesis of this syndrome (Nikolov and Illei, 2009). Several models of pathogenesis have been proposed, involving genetics, the environment, the innate and adaptive immune system, the autonomic nervous system, hormonal factors, or an interplay of these factors (Nikolov and Illei, 2009, Lessard, 2013, Burbelo et al., 2014, Iwakiri et al., 2009, Deshmukh et al., 2009, Zheng et al., 2010, Alevizos et al., 2011, Nocturne and Mariette, 2013, Gabor Illei. and Alevizos, 2013 Hernandez-Molina et al., 2011, Valtysdottir et al., 2001, Laine et al., 2007, Porola et al., 2008, Forsblad-d\'Elia et al., 2009, Cai et al., 2008, Barendregt et al., 1998, Mandl et al., 2007, Andonopoulos et al., 1998). Since first described by Henrik Sjögren, the chief oral complaint of individuals with SS most commonly has been the symptom of dry apexbio calculator or xerostomia, associated with significant morbidity and affecting the oral-health-related quality of life of patients (Sjögren, 1933, Visvanathan and Nix, 2010, Fox et al., 2008, Napenas and Rouleau, 2014, Ying Joanna and Thomson, 2015). However, patient-reported xerostomia is not an exclusive characteristic of Sjögren\'s syndrome, but could be a result of other conditions (Manuel Ramos-Casals and Moutsopoulos, 2012, Porter and Scully, 2000, Sreebny and Schwartz, 1997, Rad et al., 2010). This subjective complaint of xerostomia does not necessarily correlate with objective measures of hyposalivation (Manuel Ramos-Casals and Moutsopoulos, 2012, Fox et al., 1985, Ying Joanna and Thomson, 2015). Rather, xerostomia has been found to be associated with compositional changes of saliva (Alliende et al., 2008). Studies have also shown differences in the composition of stimulated saliva from the major salivary glands in patients with SS compared to healthy controls, and there is no correlation between compositional changes of stimulated saliva and salivary flow rates (Atkinson et al., 1990, Kalk et al., 2002, Mathews et al., 2008, Helenius et al., 2005). Xerostomia is also dependent on individual patient thresholds for oral dryness, tolerance, and adaptation (Manuel Ramos-Casals and Moutsopoulos, 2012, Scully and Felix, 2005). Recently, new classification criteria for SS have been proposed (Shiboski et al., 2012). While the current American-European consensus classification criteria for SS include xerostomia and hyposalivation in the assessment algorithm, the new classification set does not (Shiboski et al., 2012, Vitali et al., 2002). Consequently, salivary gland involvement in SS is assessed partially by the new criteria by the presence of focal lymphocytic sialadenitis (Daniels et al., 2011). Therefore, the new approach to classification has a potential for misclassification and for missing cases that are in an early stage of disease progression (Vitali et al., 2013).
Materials & Methods
Results As of August 27, 2015, the SSGDU at NIDCR/NIH has evaluated 3349 and enrolled 2046 participants. In this study, we compared baseline data of three groups at high-risk for salivary gland dysfunction with 701 SS, 355 Sicca, and 247 ISS participants (Fig. 1). Demographic characteristics of these groups were assessed, stratified by the presence or absence of xerostomia (Table 1). In the SS group, age, race and ethnicity were significantly different between those with and without xerostomia. In the Sicca group, differences in gender and ethnicity were statistically significant and in the ISS group, no differences in demographics by xerostomia status were found. The three groups, SS, Sicca, and ISS differed in the prevalence of key characteristics, i.e., xerostomia, positive focus score, and positive serology (Supporting Information (SI)), with the SS group having the highest prevalence of these characteristics. The duration of dry mouth symptoms also differed across groups with the SS group having the longest median duration (SI).