Abstract
IntroductionA growing interest has arisen in salivary proteomics as a tool for the identification of biomarkers for primary Sjögren's syndrome (pSS). Nonetheless, only a limited number of preclinical validation studies have been performed, limiting the possibility of translating proteomic results into clinical practice. The primary aim of this study was to refine the diagnostic power of a panel of candidate salivary biomarkers described in pSS with respect to both healthy volunteers and pathological controls. We also explored the pathogenetic function of the detected putative biomarkers both in the local exocrinopathy and in the systemic inflammatory processes of SS.MethodsOne hundred and eighty patients were included in the study overall. In the first "exploratory phase", we enrolled 40 females with pSS, 40 sex- and age-matched healthy volunteers, 10 patients with sicca non-SS and 15 secondary SS (sSS) patients. The testing cohort of the second "challenge phase" of the study was represented by 75 unselected, consecutive subjects: 19 pSS, 21 healthy volunteers, 10 sicca non-SS and 25 sSS patients. Salivary proteomic analysis was performed combining two-dimensional electrophoresis (2DE) and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). Western blot (WB) analysis and enzyme-linked immunosorbent assay (ELISA) were employed to validate 2DE results. Ingenuity Pathway Analysis (IPA) Knowledge base was adopted to associate candidate biomarkers in a signalling pathogenetic network.ResultsA total of 28, 6, 7 and 12 protein spots were found to be significantly different in pSS samples with respect to healthy volunteers, non-SS sicca syndrome, SSc-sSS and rheumatoid arthritis-sSS, leading to the identification of 15 differently expressed proteins. Among them, α-amylases precursor, carbonic anhydrase VI, β-2 microglobulin, glyceraldehydes-3-phosphate dehydrogenase (G3PDH), epidermal fatty acid binding protein (E-FABP) and immunoglobulin k light chain (IGK-light chain) apparently showed the most significant differences in pSS when compared to healthy volunteers and non-SS pathological controls. On the other hand, as expected, pSS and sSS salivary profiles shared a great number of similarities.ConclusionsThis study demonstrated that salivary fluid might represent a novel ideal milieu for the detection of a diagnostic panel of candidate biomarkers for pSS, and to gain an insight into the pathogenetic processes underlying glandular and systemic autoimmune disorders.
Highlights
A growing interest has arisen in salivary proteomics as a tool for the identification of biomarkers for primary Sjögren’s syndrome
A-amylases precursor, carbonic anhydrase VI, b-2 microglobulin, glyceraldehydes-3-phosphate dehydrogenase (G3PDH), epidermal fatty acid binding protein (E-FABP) and immunoglobulin k light chain (IGK-light chain) apparently showed the most significant differences in primary Sjögren’s syndrome (pSS) when compared to healthy volunteers and non-s syndrome (SS) pathological controls
Patients One hundred and eighty subjects were included in the study: 105 subjects were enrolled in the first “exploratory” phase and 75 in the second “challenge” phase
Summary
A growing interest has arisen in salivary proteomics as a tool for the identification of biomarkers for primary Sjögren’s syndrome (pSS). The complexity of SS clinical presentation is increased by the fact that SS may occur alone, as a primary condition (primary Sjögren’s syndrome-pSS), or in association with other connective tissue diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc) as secondary SS (sSS) [8,9,10]. Saliva, which may closely reflect the underlying pathogenetic process in salivary glands, has been viewed as an attractive biofluid for proteomic research in pSS and a number of studies have so far outlined the potential differences between pSS and healthy controls [11,12,13,14,15,16,17]. The pattern of identified proteins was not preclinically validated
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