PMID- 22117835 OWN - NLM STAT- MEDLINE DCOM- 20121214 LR - 20220409 IS - 1478-6362 (Electronic) IS - 1478-6354 (Print) IS - 1478-6354 (Linking) VI - 13 IP - 6 DP - 2011 TI - Proteomic analysis of saliva: a unique tool to distinguish primary Sjogren's syndrome from secondary Sjogren's syndrome and other sicca syndromes. PG - R194 LID - 10.1186/ar3523 [doi] AB - INTRODUCTION: A growing interest has arisen in salivary proteomics as a tool for the identification of biomarkers for primary Sjogren'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. METHODS: One 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. RESULTS: A 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, alpha-amylases precursor, carbonic anhydrase VI, beta-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. CONCLUSIONS: This 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. FAU - Baldini, Chiara AU - Baldini C AD - Department of Internal Medicine, Rheumatology Unit, University of Pisa, Via Roma 67, 56126 Pisa, Italy. FAU - Giusti, Laura AU - Giusti L FAU - Ciregia, Federica AU - Ciregia F FAU - Da Valle, Ylenia AU - Da Valle Y FAU - Giacomelli, Camillo AU - Giacomelli C FAU - Donadio, Elena AU - Donadio E FAU - Sernissi, Francesca AU - Sernissi F FAU - Bazzichi, Laura AU - Bazzichi L FAU - Giannaccini, Gino AU - Giannaccini G FAU - Bombardieri, Stefano AU - Bombardieri S FAU - Lucacchini, Antonio AU - Lucacchini A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111125 PL - England TA - Arthritis Res Ther JT - Arthritis research & therapy JID - 101154438 RN - 0 (Immunoglobulin Light Chains) RN - 0 (Immunoglobulin kappa-Chains) RN - 0 (Proteome) RN - 0 (beta 2-Microglobulin) RN - EC 3.2.1.1 (alpha-Amylases) RN - EC 4.2.1.11 (Phosphopyruvate Hydratase) SB - IM MH - Adult MH - Aged MH - Arthritis, Rheumatoid/complications MH - Blotting, Western MH - Case-Control Studies MH - Cluster Analysis MH - Diagnosis, Differential MH - Electrophoresis, Gel, Two-Dimensional MH - Female MH - Humans MH - Immunoglobulin Light Chains/metabolism MH - Immunoglobulin kappa-Chains/metabolism MH - Middle Aged MH - Models, Biological MH - Phosphopyruvate Hydratase/metabolism MH - Principal Component Analysis MH - Proteome/*analysis MH - Proteomics/*methods MH - Saliva/*metabolism MH - Scleroderma, Systemic/complications MH - Signal Transduction MH - Sjogren's Syndrome/diagnosis/etiology/*metabolism MH - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization MH - alpha-Amylases/metabolism MH - beta 2-Microglobulin/metabolism PMC - PMC3334644 EDAT- 2011/11/29 06:00 MHDA- 2012/12/15 06:00 PMCR- 2011/11/25 CRDT- 2011/11/29 06:00 PHST- 2011/05/23 00:00 [received] PHST- 2011/07/06 00:00 [revised] PHST- 2011/11/25 00:00 [accepted] PHST- 2011/11/29 06:00 [entrez] PHST- 2011/11/29 06:00 [pubmed] PHST- 2012/12/15 06:00 [medline] PHST- 2011/11/25 00:00 [pmc-release] AID - ar3523 [pii] AID - 10.1186/ar3523 [doi] PST - ppublish SO - Arthritis Res Ther. 2011;13(6):R194. doi: 10.1186/ar3523. Epub 2011 Nov 25.