{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:57:00Z","timestamp":1784653020607,"version":"3.55.0"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Proteomic techniques are useful to analyse the periodontal proteome in gingival crevicular fluid (GCF) and saliva. However, few investigations have assessed and compared the GCF and salivary proteomes. Therefore, this research aims to analyse the proteome structure and compare protein expression in these fluids between individuals with periodontal health and those with periodontitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>GCF and saliva were collected from 44 periodontally healthy subjects and 41 with periodontitis (stages III-IV). Samples were analysed using sequential window acquisition of all theoretical mass spectra (SWATH-MS), and proteins were identified employing the UniProt database. The periodontal proteome structure was assessed using principal component analysis (PCA). Differential protein expression was defined as an adjusted p-value &amp;lt;0.05 combined with a fold-change \u22652 (upregulated) or \u22640.5 (downregulated).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>250 abundant proteins were quantified in GCF and 377 in saliva (238 in common). The proteome structure was different in periodontitis compared to periodontal health in both oral fluids. In GCF, 63 (25.2%) proteins were differentially expressed, with 38 upregulated and 25 downregulated in periodontitis. The most overexpressed proteins were haemoglobin subunits (Hbs) beta (fold-change of 5.06) and alpha (4.35), carbonic anhydrase 1 (4.28), and protein S100-P (4.27). Among the underexpressed proteins, 14 were keratins, with type II cytoskeletal 6B being the most downregulated (0.10), together with glyceraldehyde-3-phosphate dehydrogenase (0.12) and zymogen granule protein 16 homolog B (0.13).<\/jats:p><jats:p>In saliva, 59 (15.7%) proteins were differentially expressed, with 55 upregulated and four downregulated in periodontitis. Twenty-nine proteins showed a fold-change \u22654, highlighting beta-2-microglobulin (44.14), keratin, type I cytoskeletal 13 (36.23), neutrophil defensin 1 (25.08), proteins S100-A9 (12.30), A8 (10.61), A12 (4.76), and P (4.72), annexin A1 (9.34), lysozyme C (4.98), immunoglobulin heavy constant alpha 1 (4.45), resistin (4.37), and Hbs beta (4.20) and alpha (4.06). The most downregulated protein was lipocalin-1 (0.35). Fourteen proteins were differentially expressed in GCF and saliva, where seven were keratins being underexpressed in GCF but overexpressed in saliva.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Periodontitis alters the periodontal proteome structure and the expression of numerous abundant proteins in GCF and saliva. However, proteins expressed vary qualitatively and quantitatively, indicating different expression patterns between oral fluids.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1576906","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:52:04Z","timestamp":1746186724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterisation of the periodontal proteome in gingival crevicular fluid and saliva using SWATH-MS"],"prefix":"10.3389","volume":"15","author":[{"given":"Triana","family":"Blanco-Pintos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Regueira-Iglesias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berta","family":"Su\u00e1rez-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelia","family":"Seijas-Otero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Relvas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana B.","family":"Bravo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Balsa-Castro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Tom\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/978-1-4939-3106-4_7","article-title":"False discovery rate estimation in proteomics","volume":"1362","author":"Aggarwal","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00620","article-title":"CD5L, macrophage apoptosis inhibitor, was identified in epicardial fat-secretome and regulated by isoproterenol from patients with heart failure","volume":"11","author":"Agra-Bermejo","year":"2020","journal-title":"Front. Physiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/jre.13313","article-title":"Progression from healthy periodontium to gingivitis and periodontitis: Insights from bioinformatics-driven proteomics - A systematic review with meta-analysis","volume":"60","author":"Ahmad","year":"2025","journal-title":"J. Periodontal. Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22010226","article-title":"Characterization of new proteomic biomarker candidates in mucopolysaccharidosis Type IVA","volume":"22","author":"\u00c1lvarez","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1442-9993.2001.01070.pp.x","article-title":"A new method for non-parametric multivariate analysis of variance","volume":"26","author":"Anderson","year":"2001","journal-title":"Austral. Ecol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1600278","DOI":"10.1002\/pmic.201600278","article-title":"SWATH-MS as a tool for biomarker discovery: From basic research to clinical applications","volume":"17","author":"Anjo","year":"2017","journal-title":"Proteomics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.abb.2018.01.004","article-title":"Myeloperoxidase: Its role for host defense, inflammation, and neutrophil function","volume":"640","author":"Aratani","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"B8","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1111\/j.1600-051X.2011.01805.x","article-title":"Novel protein identification methods for biomarker discovery via a proteomic analysis of periodontally healthy and diseased gingival crevicular fluid samples","volume":"39","author":"Baliban","year":"2012","journal-title":"J. Clin. Periodontol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/B978-0-12-386471-0.00004-3","article-title":"Serpins and the complement system","volume":"499","author":"Beinrohr","year":"2011","journal-title":"Methods Enzymol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/ma15062161","article-title":"Proteomics disclose the potential of gingival crevicular fluid (GCF) as a source of biomarkers for severe periodontitis","volume":"15","author":"Bellei","year":"2022","journal-title":"Materials"},{"key":"B11","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc B. Stat. Methodol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1111\/j.1423-0410.1980.tb04500.x","article-title":"\u03b22-microglobulin: Structure, function and significance","volume":"38","author":"Bernier","year":"1980","journal-title":"Vox. Sang."},{"key":"B13","doi-asserted-by":"publisher","first-page":"6259","DOI":"10.3390\/ijms14036259","article-title":"Annexin A2 heterotetramer: structure and function","volume":"14","author":"Bharadwaj","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1002\/JPER.24-0062","article-title":"Impact of smoking habit on the subgingival proteome in patients with periodontitis","volume":"96","author":"Blanco-Pintos","year":"2025","journal-title":"J. Periodontol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/jcpe.14103","article-title":"Diagnostic accuracy of novel protein biomarkers in saliva to detect periodontitis using untargeted \u2018SWATH\u2019 mass spectrometry","volume":"52","author":"Blanco-Pintos","year":"2025","journal-title":"J. Clin. Periodontol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1111\/jcpe.14037","article-title":"Using SWATH-MS to identify new molecular biomarkers in gingival crevicular fluid for detecting periodontitis and its response to treatment","volume":"51","author":"Blanco-Pintos","year":"2024","journal-title":"J. Clin. Periodontol."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.003335","article-title":"A robust method for quantitative high-throughput analysis of proteomes by 18O labeling","volume":"10","author":"Bonzon-Kulichenko","year":"2011","journal-title":"Mol. Cell. Proteomics"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1500518","DOI":"10.1002\/pmic.201500518","article-title":"Contribution of proteomics to our understanding of periodontal inflammation","volume":"17","author":"Bostanci","year":"2017","journal-title":"Proteomics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1111\/prd.12154","article-title":"Gingival crevicular fluid and its immune mediators in the proteomic era","volume":"76","author":"Bostanci","year":"2018","journal-title":"Periodontol. 2000."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1074\/mcp.RA118.000718","article-title":"Targeted proteomics guided by label-free quantitative proteome analysis in saliva reveal transition signatures from health to periodontal disease","volume":"17","author":"Bostanci","year":"2018","journal-title":"Mol. Cell. Proteomics."},{"key":"B21","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s12017-025-08840-6","article-title":"NOTCH3 variant position affects the phenotype at the pluripotent stem cell level in CADASIL","volume":"27","author":"Bugallo-Casal","year":"2025","journal-title":"Neuromol. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1080\/14737159.2020.1743686","article-title":"Saliva as a diagnostic tool for dental caries, periodontal disease and cancer: is there a need for more biomarkers","volume":"20","author":"Buzalaf","year":"2020","journal-title":"Expert. Rev. Mol. Diagn."},{"key":"B23","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.trsl.2021.01.006","article-title":"Human obese white adipose tissue sheds depot-specific extracellular vesicles and reveals candidate biomarkers for monitoring obesity and its comorbidities","volume":"239","author":"Camino","year":"2022","journal-title":"Transl. Res."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21062252","article-title":"Vesicles shed by pathological murine adipocytes spread pathology: Characterization and functional role of insulin resistant\/hypertrophied adiposomes","volume":"21","author":"Camino","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1111\/jcpe.12262","article-title":"Quantitative gingival crevicular fluid proteome in health and periodontal disease using stable isotope chemistries and mass spectrometry","volume":"41","author":"Carneiro","year":"2014","journal-title":"J. Clin. Periodontol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/J.NBD.2024.106665","article-title":"The proteomic signature of circulating extracellular vesicles following intracerebral hemorrhage: Novel insights into mechanisms underlying recovery","volume":"201","author":"Casado-Fern\u00e1ndez","year":"2024","journal-title":"Neurobiol. Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1111\/jcpe.13803","article-title":"Salivary annexin A1: A candidate biomarker for periodontitis","volume":"50","author":"Casarin","year":"2023","journal-title":"J. Clin. Periodontol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1111\/jcpe.12935","article-title":"A new classification scheme for periodontal and peri-implant diseases and conditions \u2013 Introduction and key changes from the 1999 classification","volume":"45","author":"Caton","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2019.103581","article-title":"Proteomic investigation on bio-corona of Au, Ag and Fe nanoparticles for the discovery of triple negative breast cancer serum protein biomarkers","volume":"212","author":"Chantada-V\u00e1zquez","year":"2020","journal-title":"J. Proteomics."},{"key":"B30","volume-title":"Statistical power analysis for the behavioral sciences","author":"Cohen","year":"1988"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1002\/pmic.201400353","article-title":"Development of a highly automated and multiplexed targeted proteome pipeline and assay for 112 rat brain synaptic proteins","volume":"15","author":"Colangelo","year":"2015","journal-title":"Proteomics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41592-019-0638-x","article-title":"DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput","volume":"17","author":"Demichev","year":"2020","journal-title":"Nat. Methods"},{"key":"B33","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/prd.12323","article-title":"Recent epidemiologic trends in periodontitis in the USA","volume":"82","author":"Eke","year":"2020","journal-title":"Periodontol. 2000."},{"key":"B34","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1128\/AAC.49.1.269-275.2005","article-title":"Antibacterial activity and specificity of the six human {alpha}-defensins","volume":"49","author":"Ericksen","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"B35","doi-asserted-by":"publisher","first-page":"175","DOI":"10.3758\/bf03193146","article-title":"G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"B36","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/B978-0-444-63688-1.00009-4","article-title":"SWATH-MS: Data acquisition and analysis","volume-title":"Proteomic Profiling and Analytical Chemistry","author":"Frederick","year":"2016"},{"key":"B37","doi-asserted-by":"publisher","first-page":"498","DOI":"10.5606\/ArchRheumatol.2018.6595","article-title":"Cathepsin G and its role in inflammation and autoimmune diseases","volume":"33","author":"Gao","year":"2018","journal-title":"Arch. Rheumatol."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/nano10122370","article-title":"A novel nanoproteomic approach for the identification of molecular targets associated with thyroid tumors","volume":"10","author":"Garc\u00eda-Vence","year":"2020","journal-title":"Nanomaterials"},{"key":"B39","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1111\/jcpe.13630","article-title":"Discovery, validation, and diagnostic ability of multiple protein-based biomarkers in saliva and gingival crevicular fluid to distinguish between health and periodontal diseases","volume":"49","author":"Grant","year":"2022","journal-title":"J. Clin. Periodontol."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00208","article-title":"Oral mucosal epithelial cells","volume":"10","author":"Groeger","year":"2019","journal-title":"Front. Immunol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1111\/jcpe.13617","article-title":"Molecular biomarker research in periodontology: A roadmap for translation of science to clinical assay validation","volume":"49","author":"G\u00fcrsoy","year":"2022","journal-title":"J. Clin. Periodontol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1586\/14789450.2014.864953","article-title":"Proteomics for the discovery of biomarkers and diagnosis of periodontitis: A critical review","volume":"11","author":"Guzman","year":"2014","journal-title":"Expert. Rev. Proteomics."},{"key":"B43","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1111\/jre.12575","article-title":"High-throughput proteomic analysis of candidate biomarker changes in gingival crevicular fluid after treatment of chronic periodontitis","volume":"53","author":"Guzman","year":"2018","journal-title":"J. Periodontal. Res."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2019.103602","article-title":"Proteomic analysis of whole saliva in chronic periodontitis","volume":"213","author":"Hartenbach","year":"2020","journal-title":"J. Proteomics."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/srep35391","article-title":"Application of targeted mass spectrometry for the quantification of sirtuins in the central nervous system","volume":"6","author":"Jayasena","year":"2016","journal-title":"Sci. Rep."},{"key":"B46","unstructured":"factoextra: Extract and visualize the results of multivariate data analyses. R package\n          \n          \n            \n              Kassambara\n              A.\n            \n            \n              Mundt\n              F.\n            \n          \n          \n          2020"},{"key":"B47","doi-asserted-by":"publisher","first-page":"123","DOI":"10.3892\/mmr.2020.11762","article-title":"Identification of galectin-10 as a biomarker for periodontitis based on proteomic analysis of gingival crevicular fluid","volume":"23","author":"Kim","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"B48","doi-asserted-by":"publisher","first-page":"17039","DOI":"10.1038\/nrdp.2017.38","article-title":"Periodontal diseases","volume":"3","author":"Kinane","year":"2017","journal-title":"Nat. Rev. Dis. Primers."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v025.i01","article-title":"FactoMineR: An R package for multivariate analysis","volume":"25","author":"L\u00ea","year":"2008","journal-title":"J. Stat. Software"},{"key":"B50","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.trsl.2024.02.006","article-title":"Characterization of the plasma proteomic profile of Fabry disease: Potential sex- and clinical phenotype-specific biomarkers","volume":"269","author":"L\u00f3pez-Valverde","year":"2024","journal-title":"Transl. Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e8126","DOI":"10.15252\/msb.20178126","article-title":"Data-independent acquisition-based SWATH-MS for quantitative proteomics: a tutorial","author":"Ludwig","year":"2018","journal-title":"Mol. Syst. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1111\/odi.12996","article-title":"Quantitative gingival crevicular fluid proteome in type 2 diabetes mellitus and chronic periodontitis","volume":"25","author":"Marinho","year":"2019","journal-title":"Dis."},{"key":"B53","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.ijbiomac.2020.12.073","article-title":"Role of immunoglobulin and antibodies in disease management","volume":"169","author":"Megha","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"907078","DOI":"10.1155\/2012\/907078","article-title":"The role of S100A12 as a systemic marker of inflammation","volume":"2012","author":"Meijer","year":"2012","journal-title":"Int. J. Inflam."},{"key":"B55","doi-asserted-by":"publisher","first-page":"35","DOI":"10.4155\/bio-2017-0218","article-title":"Assessing a multiplex-targeted proteomics approach for the clinical diagnosis of periodontitis using saliva samples","volume":"10","author":"Mertens","year":"2018","journal-title":"Bioanalysis"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/J.MCPRO.2024.100834","article-title":"Identification of a proteomic signature for predicting immunotherapy response in patients with metastatic non-small cell lung cancer","volume":"23","author":"Mondelo-Mac\u00eda","year":"2024","journal-title":"Mol. Cell. Proteomics."},{"key":"B57","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1111\/jcpe.12534","article-title":"Clinical research activity in periodontal medicine: A systematic mapping of trial registers","volume":"43","author":"Monsarrat","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"e42080","DOI":"10.7759\/cureus.42080","article-title":"Exploring the biological width in dentistry: A comprehensive narrative review","volume":"15","author":"Mulla","year":"2023","journal-title":"Cur\u0113us"},{"key":"B59","doi-asserted-by":"publisher","first-page":"3070","DOI":"10.4049\/jimmunol.172.5.3070","article-title":"Postsecretory processing generates multiple cathelicidins for enhanced topical antimicrobial defense","volume":"172","author":"Murakami","year":"2004","journal-title":"J. Immunol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1177\/00220345820610100901","article-title":"A comparison of whole mouth resting and stimulated salivary measurement procedures","volume":"61","author":"Navazesh","year":"1982","journal-title":"J. Dent. Res."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102071","article-title":"Impact of liver-specific GLUT8 silencing on fructose-induced inflammation and omega oxidation","volume":"24","author":"Novelle","year":"2021","journal-title":"iScience"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1097\/hep.0000000000000930","article-title":"Mitochondrial antiviral signaling protein enhances MASLD progression through the ERK\/TNF\u03b1\/NF\u03ba\u03b2 pathway","volume":"81","author":"N\u00f3voa","year":"2025","journal-title":"Hepatology"},{"key":"B63","unstructured":"vegan: Community ecology package. R package\n          \n          \n            \n              Oksanen\n              J.\n            \n            \n              Simpson\n              G.\n            \n            \n              Blanchet\n              F.\n            \n            \n              Kindt\n              R.\n            \n            \n              Legendre\n              P.\n            \n            \n              Minchin\n              P.\n            \n          \n          \n          2022"},{"key":"B64","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.imbio.2006.02.004","article-title":"Iron-withholding strategy in innate immunity","volume":"211","author":"Ong","year":"2006","journal-title":"Immunobiology"},{"key":"B65","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.jprot.2018.01.003","article-title":"Identification of candidate serum biomarkers of childhood-onset growth hormone deficiency using SWATH-MS and feature selection","volume":"175","author":"Ortea","year":"2018","journal-title":"J. Proteomics."},{"key":"B66","doi-asserted-by":"publisher","first-page":"11649","DOI":"10.1074\/jbc.M112.445304","article-title":"The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes","volume":"288","author":"Perez-Hernandez","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B67","volume-title":"R: A language and environment for statistical computing","year":"2022"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e04022","article-title":"Proteomics approach for biomarkers and diagnosis of periodontitis: systematic review","volume":"6","author":"Rizal","year":"2020","journal-title":"Heliyon"},{"key":"B69","doi-asserted-by":"publisher","first-page":"3736","DOI":"10.1038\/s41467-024-47751-1","article-title":"dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe","volume":"15","author":"Rodrigues","year":"2024","journal-title":"Nat. Commun."},{"key":"B70","doi-asserted-by":"publisher","first-page":"140031","DOI":"10.1038\/sdata.2014.31","article-title":"A repository of assays to quantify 10,000 human proteins by SWATH-MS","volume":"1","author":"Rosenberger","year":"2014","journal-title":"Sci. Data."},{"key":"B71","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1111\/jcpe.12130","article-title":"Identification of periodontitis associated changes in the proteome of whole human saliva by mass spectrometric analysis","volume":"40","author":"Salazar","year":"2013","journal-title":"J. Clin. Periodontol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1128\/MCB.23.5.1509-1519.2003","article-title":"Transcript-selective translational silencing by gamma interferon is directed by a novel structural element in the ceruloplasmin mRNA 3\u2032 untranslated region","volume":"23","author":"Sampath","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1021\/ac950914h","article-title":"Mass spectrometric sequencing of proteins from silver-stained polyacrylamide gels","volume":"68","author":"Shevchenko","year":"1996","journal-title":"Anal. Chem."},{"key":"B74","doi-asserted-by":"publisher","first-page":"3571","DOI":"10.1007\/s00784-018-2779-1","article-title":"Deep sequencing salivary proteins for periodontitis using proteomics","volume":"23","author":"Shin","year":"2019","journal-title":"Clin.  Invest."},{"key":"B75","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1111\/jcpe.13990","article-title":"Probing the salivary proteome for prognostic biomarkers in response to non-surgical periodontal therapy","volume":"52","author":"Silbereisen","year":"2024","journal-title":"J. Clin. Periodontol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"e75898","DOI":"10.1371\/journal.pone.0075898","article-title":"Quantitative proteomic analysis of gingival crevicular fluid in different periodontal conditions","volume":"8","author":"Silva-Boghossian","year":"2013","journal-title":"PloS One"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2015.00187","article-title":"Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders","volume":"6","author":"Smith","year":"2015","journal-title":"Front. Physiol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1189\/jlb.0808495","article-title":"Neutrophil-derived azurocidin alarms the immune system","volume":"85","author":"Soehnlein","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"e1004446","DOI":"10.1371\/journal.ppat.1004446","article-title":"The ESAT-6 protein of Mycobacterium tuberculosis interacts with beta-2-microglobulin (\u03b22M) affecting antigen presentation function of macrophage","volume":"10","author":"Sreejit","year":"2014","journal-title":"PloS Pathog."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.585399","article-title":"Ribosomal protein SA-positive neutrophil elicits stronger phagocytosis and neutrophil extracellular trap formation and subdues pro-inflammatory cytokine secretion against Streptococcus suis serotype 2 infection","volume":"11","author":"Sun","year":"2021","journal-title":"Front. Immunol."},{"key":"B81","first-page":"CR66","article-title":"Lysozyme and microbiota in relation to gingivitis and periodontitis","volume":"15","author":"Surna","year":"2009","journal-title":"Med. Sci. Monit."},{"key":"B82","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.cca.2019.04.076","article-title":"The potentiality of salivary peptide biomarkers for screening patients with periodontal diseases by mass spectrometry","volume":"495","author":"Tang","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"B83","volume-title":"mutoss: Unified multiple testing procedures","author":"Team","year":"2023"},{"key":"B84","doi-asserted-by":"publisher","first-page":"3334","DOI":"10.1074\/jbc.M109744200","article-title":"Glyceraldehyde-3-phosphate dehydrogenase is phosphorylated by protein kinase ciota\/lambda and plays a role in microtubule dynamics in the early secretory pathway","volume":"277","author":"Tisdale","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B85","doi-asserted-by":"publisher","first-page":"S149","DOI":"10.1111\/jcpe.12945","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition","volume":"45","author":"Tonetti","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"B86","volume-title":"effsize: Efficient effect size computation","author":"Torchiano","year":"2020"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251910761","article-title":"Differential protein expression in extracellular vesicles defines treatment responders and non-responders in multiple sclerosis","volume":"25","author":"Torres Iglesias","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B88","doi-asserted-by":"publisher","first-page":"3141","DOI":"10.1111\/febs.15322","article-title":"Resistin in metabolism, inflammation, and disease","volume":"287","author":"Tripathi","year":"2020","journal-title":"Febs. J."},{"key":"B89","doi-asserted-by":"publisher","first-page":"D191","DOI":"10.1093\/nar\/gkt1140","article-title":"Activities at the universal protein resource (UniProt)","volume":"42","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B90","doi-asserted-by":"publisher","first-page":"3005","DOI":"10.1111\/all.16327","article-title":"Exploring CD26\u2013\/lo subpopulations of lymphocytes in asthma phenotype and severity: A novel CD4+ T cell subset expressing archetypical granulocyte proteins","volume":"79","author":"V\u00e1zquez-Mera","year":"2024","journal-title":"Allergy"},{"key":"B91","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.cyto.2016.03.015","article-title":"Alarmin human \u03b1 defensin HNP1 activates plasmacytoid dendritic cells by triggering NF-\u03baB and IRF1 signaling pathways","volume":"83","author":"Wang","year":"2016","journal-title":"Cytokine"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01298","article-title":"S100A8\/A9 in inflammation","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Immunol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World medical association declaration of Helsinki: Ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"JAMA"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2020.121956","article-title":"Direct MALDI-TOF profiling of gingival crevicular fluid sediments for periodontitis diagnosis","volume":"225","author":"Yi","year":"2021","journal-title":"Talanta"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2021.104421","article-title":"A comparative proteomic analysis to define the influencing factors on gingival crevicular fluid using LC-MS\/MS","volume":"252","author":"Zhang","year":"2022","journal-title":"J. Proteomics."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1576906\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:52:11Z","timestamp":1746186731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1576906\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,2]]},"references-count":95,"alternative-id":["10.3389\/fcimb.2025.1576906"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1576906","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,2]]},"article-number":"1576906"}}