Biomarker profiles in serum and saliva of experimental Sjögren's syndrome: associations with specific autoimmune manifestations

Abstract

Introduction Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly targets the exocrine glands. The aim of this study was to investigate the involvement of 87 proteins measured in serum and 75 proteins analyzed in saliva in spontaneous experimental SS. In addition, we intended to compute a model of the immunological situation representing the overt disease stage of SS. Methods Nondiabetic, nonobese diabetic (NOD) mice aged 21 weeks were evaluated for salivary gland function, salivary gland inflammation and extraglandular disease manifestations. The analytes, comprising chemokines, cytokines, growth factors, autoantibodies and other biomarkers, were quantified using multi-analyte profile technology and fluorescence-activated cell sorting. Age-matched and sex-matched Balb/c mice served as a reference. Results We found NOD mice to exhibit impaired salivary flow, glandular inflammation and increased secretory SSB (anti-La) levels. Thirty-eight biomarkers in serum and 34 in saliva obtained from NOD mice were significantly different from those in Balb/c mice. Eighteen biomarkers in serum and three chemokines measured in saliva could predict strain membership with 80% to 100% accuracy. Factor analyses identified principal components mostly correlating with one clinical aspect of SS and having distinct associations with components extracted from other families of proteins. Conclusion Autoimmune manifestations of SS are greatly independent and associated with various immunological processes. However, CD40, CD40 ligand, IL-18, granulocyte chemotactic protein-2 and anti-muscarinic M3 receptor IgG 3 may connect the different aspects of SS. Processes related to the adaptive immune system appear to promote SS with a strong involvement of T-helper-2 related proteins in hyposalivation. This approach further established saliva as an attractive biofluid for biomarker analyses in SS and provides a basis for the comparison and selection of potential drug targets and diagnostic markers.

Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression in salivary glands as one endogenous modulator of acinar cell apoptosis in a murine model of Sjögren's syndrome

“…This observation supports the hypothesis that acinar cells are involved actively in the pathogenesis of SS and provides new evidence to the search of early biomarkers for diagnosis and/or disease activity. At the prediabetic stage, the non-obese diabetic (NOD) mouse model of Sjögren's syndrome has the unique characteristic of developing a deep secretory dysfunction with mild infiltration of the glands [9][10][11] consistent with a structural-dysfunctional aetiology. In keeping with this, early neurotransmitter receptor-signalling alterations have been reported in NOD females' submandibular glands unrelated to the onset of the autoimmune response [12][13][14].…”

Characterization of Angiogenesis and Lymphangiogenesis in Human Minor Salivary Glands with Sjögren’s Syndrome

“…This observation suggests that a remodeling of the vasculature in the salivary glands may not be necessary to facilitate chronic hyperemia. Additionally, reported findings on protein expression levels of vascular endothelial growth factor (VEGF, an initiator of angiogenesis) have been contradictory, with some studies displaying an increase (Ohno et al 2004;Sisto et al 2012) and others no change or a decrease in expression (Delaleu et al 2008;Szodoray et al 2004).…”

“…Interestingly, it has been shown that some patients with SS have increased blood flow (hyperemia) through their major salivary glands, as compared with that of healthy 573323J HCXXX10.1369/0022155415573323McCall and BakerAngiogenesis in Sjögren's Syndrome research-article2015 individuals (Chikui et al 2000;Steiner et al 1994). This finding is suggestive of blood vessel growth and remodeling (angiogenesis), and has led to numerous studies investigating pro-angiogenic factors in patients with SS (Delaleu et al 2008;Ohno et al 2004;Sisto et al 2012;Szodoray et al 2004). However, no previous studies have directly analyzed the vascular organization of salivary glands with SS for signs of angiogenesis.…”

Dental perspective on Sjögren’s syndrome: literature review

“…PATHOGENESIS SS is characterized by epithelial cell destruction and peri-epithelial infiltration by T CD4 lymphocytes and a lower number of B lymphocytes 14 with multiple target organs, particularly exocrine glands. Th2 cytokines have been found to be involved in an early stage of the disease, while Th1 cytokines appear at an advanced stage 15 .…”