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      Combined serum anti-SSA/Ro and salivary TRIM29 reveals promising high diagnostic accuracy in patients with primary Sjögren’s syndrome

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          Abstract

          Objectives

          To determine the diagnostic potential of simultaneous presence of serum anti-SSA/Ro and upregulated salivary protein biomarkers in patients with primary Sjögren’s syndrome (pSS).

          Methods

          Previous proteomics data on the intensity of neutrophil elastase, calreticulin, tripartite motif containing protein 29 (TRIM29), clusterin and vitronectin provided basis for performing extended analysis. Protein data was obtained by liquid chromatography tandem mass spectrometry technique in whole saliva from 24 patients with pSS and 16 patients having symptoms of pSS, but not fulfilling the American College of Rheumatology/European League against Rheumatism classification criteria (non-pSS). Serum anti-SSA/Ro antibody was measured using enzyme-linked immunosorbent assays. Receiver operating characteristic curve (ROC) value was calculated for combined biomarkers.

          Results

          Simultaneous presence of serum anti-SSA/Ro and upregulated salivary TRIM29 provided the most optimal combination with an area under curve (AUC) of 0.995 (95% CI 0.98–1.00, p = 2.0E-7 and standard error 0.007) and combinations of sensitivity and specificity within the interval of 91–100%. ROC analysis showed that salivary levels of TRIM29 alone enabled differentiation between pSS and non-pSS with an area under curve (AUC) of 0.88 (95%CI 0.77–1.00). All patients with pSS and 3 non-pSS patients were serum anti-SSA/Ro positive.

          Conclusions

          Simultaneous presence of serum anti-SSA/Ro and upregulated salivary TRIM29 provided a high diagnostic accuracy exceeding that of currently available tools used in pSS diagnostics. This biomarker combination represents a promising less invasive diagnostic tool for pSS. The clinical applicability of TRIM29 needs further testing in independent cohorts using relevant analytical techniques.

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          Most cited references17

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          2016 update of the PRIDE database and its related tools

          The PRoteomics IDEntifications (PRIDE) database is one of the world-leading data repositories of mass spectrometry (MS)-based proteomics data. Since the beginning of 2014, PRIDE Archive (http://www.ebi.ac.uk/pride/archive/) is the new PRIDE archival system, replacing the original PRIDE database. Here we summarize the developments in PRIDE resources and related tools since the previous update manuscript in the Database Issue in 2013. PRIDE Archive constitutes a complete redevelopment of the original PRIDE, comprising a new storage backend, data submission system and web interface, among other components. PRIDE Archive supports the most-widely used PSI (Proteomics Standards Initiative) data standard formats (mzML and mzIdentML) and implements the data requirements and guidelines of the ProteomeXchange Consortium. The wide adoption of ProteomeXchange within the community has triggered an unprecedented increase in the number of submitted data sets (around 150 data sets per month). We outline some statistics on the current PRIDE Archive data contents. We also report on the status of the PRIDE related stand-alone tools: PRIDE Inspector, PRIDE Converter 2 and the ProteomeXchange submission tool. Finally, we will give a brief update on the resources under development ‘PRIDE Cluster’ and ‘PRIDE Proteomes’, which provide a complementary view and quality-scored information of the peptide and protein identification data available in PRIDE Archive.
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            2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: A consensus and data-driven methodology involving three international patient cohorts.

            To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS.
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              TRIM family proteins and their emerging roles in innate immunity.

              The superfamily of tripartite motif-containing (TRIM) proteins is conserved throughout the metazoan kingdom and has expanded rapidly during vertebrate evolution; there are now more than 60 TRIM proteins known in humans and mice. Many TRIM proteins are induced by type I and type II interferons, which are crucial for many aspects of resistance to pathogens, and several are known to be required for the restriction of infection by lentiviruses. In this Review, we describe recent data that reveal broader antiviral and antimicrobial activities of TRIM proteins and discuss their involvement in the regulation of pathogen-recognition and transcriptional pathways in host defence.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 October 2021
                2021
                : 16
                : 10
                : e0258428
                Affiliations
                [1 ] Faculty of Health and Medical Sciences, Department of Odontology, Section for Oral Biology and Immunopathology, University of Copenhagen, Copenhagen, Denmark
                [2 ] Faculty of Health and Medical Sciences, Department of Odontology, Section for Clinical Oral Microbiology, University of Copenhagen, Copenhagen, Denmark
                [3 ] Department of Rheumatology, Frederiksberg Hospital, Frederiksberg, Denmark
                National Institute of Dental and Craniofacial Research, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-7808-4740
                Article
                PONE-D-21-14717
                10.1371/journal.pone.0258428
                8500413
                34624052
                45b4fc44-62eb-4e70-bea0-513c6b9b33a9
                © 2021 Sembler-Møller et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 4 May 2021
                : 27 September 2021
                Page count
                Figures: 3, Tables: 4, Pages: 10
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Saliva
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Saliva
                Biology and Life Sciences
                Physiology
                Body Fluids
                Saliva
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Research and Analysis Methods
                Immunologic Techniques
                Immunoassays
                Enzyme-Linked Immunoassays
                Physical Sciences
                Physics
                Classical Mechanics
                Continuum Mechanics
                Fluid Mechanics
                Fluid Dynamics
                Flow Rate
                Biology and Life Sciences
                Anatomy
                Digestive System
                Salivary Glands
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Salivary Glands
                Biology and Life Sciences
                Anatomy
                Exocrine Glands
                Salivary Glands
                Medicine and Health Sciences
                Anatomy
                Exocrine Glands
                Salivary Glands
                Biology and Life Sciences
                Biochemistry
                Proteins
                Chaperone Proteins
                Biology and Life Sciences
                Biochemistry
                Proteins
                Extracellular Matrix Proteins
                Biology and life sciences
                Organisms
                Viruses
                DNA viruses
                Herpesviruses
                Epstein-Barr virus
                Biology and life sciences
                Microbiology
                Medical microbiology
                Microbial pathogens
                Viral pathogens
                Herpesviruses
                Epstein-Barr virus
                Medicine and health sciences
                Pathology and laboratory medicine
                Pathogens
                Microbial pathogens
                Viral pathogens
                Herpesviruses
                Epstein-Barr virus
                Biology and life sciences
                Organisms
                Viruses
                Viral pathogens
                Herpesviruses
                Epstein-Barr virus
                Custom metadata
                The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD016231.

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                Uncategorized

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