The Potential of Salivary Proteome in Laboratory Analysis of Sjogren's Syndrome

Abstract

Detection of pathological processes at an early stage can significantly affect the clinical course and outcome of the disease, and hence the choice of appropriate therapeutic intervention. In order to achieve this and avoid invasive sampling procedures like surgical biopsy and repeated phlebotomies which introduce additional stress and safety issues in patients, research is greatly focused on identifying alternative samples and novel biomarkers for advanced laboratory analysis. Since many oral but also systemic pathological processes are being reflected in the salivary composition, it is getting increasing attention as an alternative sample to blood, especially for some population groups like children, adolescents, geriatric or psychiatric patients, where blood sampling is often compromised by insufficient cooperation from the patients or individual factors related to the patiens’ health. Sjögren's syndrome (SS) is an autoimmune disease with an insidious onset, variable course and clinical presentation, so its diagnosis is usually established about 6 years after the initiation of the disease and based on the detection and quantification of circulating autoantibodies such as: anti-Ro/SSA, anti-La/SSB, anti-muscarinic receptor antibodies, anti-nuclear antibodies and rheumatoid factor. Apart from molecular diagnostics and nanotechnology, several new approaches emerge for detecting even subtle alterations of the salivary constituents, like proteins which are employed in the proteomic analysis. Numerous proteomic studies involving sophisticated methodology like LC-MS/MS have identified aberrant expression of specific proteins in saliva of SS patients, making them potential markers of the disease and indicators of progression. Beside cytokines, many other proteins involved in the inflammatory process are upregulated vs proteins associated with the salivary production which are downregulated. Further to changes in salivary concentrations of MMP9, Complement factor B, Azurocydin Kallikrein, many other proteins including proteases like Trypsin, Catepsin, and Myeloblastin, inhibitors of Cystein proteases, Calreticulin, Protein 29, α-amylase precursor of carbonanhydrase VI, β-2 microglobulin, enolase etc. have shown aberrant expression in saliva from SS patients and a recent study has even proposed the combination of serum anti-SSA/Ro and upregulated salivary TRIM29, as an optimal marker with high diagnostic accuracy for fast and noninvasive diagnosis of SS. But, in patients with SS, efficient saliva collection is difficult because saliva secretion is significantly reduced. Therefore, when examining