Is GRP78/BiP a potential salivary biomarker in patients with rheumatoid arthritis?

Giusti, Laura; Baldini, Chiara; Ciregia, Federica; Giannaccini, Gino; Giacomelli, Camillo; Feo, Francesca De; Sedie, Andrea Delle; Riente, Lucrezia; Lucacchini, Antonio; Bazzichi, Laura; Bombardieri, Stefano

doi:10.1002/prca.200900082

Cited by 48 publications

(31 citation statements)

References 49 publications

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“…Similar trends were also reported for lipocalin and for many spots of calgranulin B (S100-A9) which showed the highest levels in RA-sSS patients. Intriguingly, since increased levels of all these proteins have been already reported in biological fluids of patients with RA without sSS [26,27], we speculated that proteomic analysis of whole saliva could represent a novel technique not only for the diagnosis of disorders involving salivary glands but also for systemic autoimmune disorders even in the absence of any salivary exocrinopathy. In line with this work hypothesis, we also found, in this study, that the salivary profile of patients with SSc-sSS, was characterised by a significant increase of G3PDH, which has been already described in whole saliva of patients with SSc without sSS [28].…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of saliva: a unique tool to distinguish primary Sjögren's syndrome from secondary Sjögren's syndrome and other sicca syndromes

et al. 2011

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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.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of saliva: a unique tool to distinguish primary Sjögren's syndrome from secondary Sjögren's syndrome and other sicca syndromes

et al. 2011

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“…The incorporation of additional non-invasive diagnostics, such as screening for disease-specific biomarkers [12, 13] has therefore been in focus over recent decades, as it can also be applied for staging and monitoring of the disease. Indeed, liquid chromatography-mass spectrometry (LC-MS) has been applied in several human rheumatic diseases, including SS, in order to discover biomarkers and therapeutic targets by studying the proteome of biological fluids [14, 15]. Both saliva [14, 16–21] and tear fluid [22, 23] have previously been used to identify potential biomarkers for SS.…”

Section: Introductionmentioning

confidence: 99%

Identification of potential saliva and tear biomarkers in primary Sjögren’s syndrome, utilising the extraction of extracellular vesicles and proteomics analysis

et al. 2017

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BackgroundThere is a long-lasting need for non-invasive, more accurate diagnostic techniques when evaluating primary Sjögren’s syndrome (pSS) patients. Incorporation of additional diagnostics involving screening for disease-specific biomarkers in biological fluid is a promising concept that requires further investigation. In the current study we aimed to explore novel disease biomarkers in saliva and tears from pSS patients.MethodsLiquid chromatography-mass spectrometry (LC-MS) was performed on stimulated whole saliva and tears from 27 pSS patients and 32 healthy controls, and salivary and tear proteomic biomarker profiles were generated. LC-MS was also combined with size exclusion chromatography to isolate extracellular vesicles (EVs) from both fluids. Nanoparticle tracking analysis was conducted on joint fractions from the saliva and tears to determine size distribution and concentration of EVs. Further EV characterisation was performed by immunoaffinity capture of CD9-positive EVs using magnetic beads, detected by flow cytometry. The LC-MS data were analysed for quantitative differences between patient and control groups using Scaffold, and the proteins were further analysed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), for gene ontology overrepresentation, and the Search Tool for the Retrieval of Interacting Genes/Proteins for protein-protein interaction network analysis.ResultsUpregulation of proteins involved in innate immunity (LCN2), cell signalling (CALM) and wound repair (GRN and CALML5) were detected in saliva in pSS. Saliva EVs also displayed biomarkers critical for activation of the innate immune system (SIRPA and LSP1) and adipocyte differentiation (APMAP). Tear analysis indicated overexpression of proteins involved in TNF-α signalling (CPNE1) and B cell survival (PRDX3). Moreover, neutrophil gelatinase-associated lipocalin was upregulated in saliva and tears in pSS. Consistently, DAVID analysis demonstrated pathways of the adaptive immune response in saliva, of cellular component assembly for saliva EVs, and of metabolism and protein folding in tears in pSS patients.ConclusionsLC-MS of saliva and tears from pSS patients, solely and in combination with size-exclusion chromatography allowed screening for possible novel biomarkers encompassing both salivary and lacrimal disease target organs. This approach could provide additional diagnostic accuracy in pSS, and could possibly also be applied for staging and monitoring the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1228-x) contains supplementary material, which is available to authorized users.

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“…These proteins have already been found in autoinflammatory rheumatic diseases such as Sjögren Syndrome, Scleroderma, and Rheumatoid Arthritis (De Seny et al, 2008;Giusti et al, 2007aGiusti et al, , 2007bGiusti et al, , 2010. Considering that fibromyalgia is defined as a non-inflammatory disease, we suggested that the over-expression of calgranulins might be related to a sub-inflammatory process, as suggested by the cytokine alterations.…”

Section: Wwwintechopencommentioning

confidence: 53%

Diagnosis of Fibromyalgia Syndrome: Potential Biomarkers and Proteomic Approach

Ciregia¹,

Giacomelli²,

Giusti³

et al. 2012

New Insights Into Fibromyalgia

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Is GRP78/BiP a potential salivary biomarker in patients with rheumatoid arthritis?

Abstract: This study provides a rationale for further studies aimed at evaluating any correlation between GRP78/BiP and different clinical/serological aspects of the disease in order to improve the diagnostic algorithms of RA.

Cited by 48 publications

References 49 publications

Proteomic analysis of saliva: a unique tool to distinguish primary Sjögren's syndrome from secondary Sjögren's syndrome and other sicca syndromes

Proteomic analysis of saliva: a unique tool to distinguish primary Sjögren's syndrome from secondary Sjögren's syndrome and other sicca syndromes

Identification of potential saliva and tear biomarkers in primary Sjögren’s syndrome, utilising the extraction of extracellular vesicles and proteomics analysis

Diagnosis of Fibromyalgia Syndrome: Potential Biomarkers and Proteomic Approach

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