{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:17:49Z","timestamp":1790720269524,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Systemic lupus erythematosus (SLE) is one of the most prevalent systemic autoimmune diseases, characterized by aberrant activation of the immune system that leads to diverse clinical symptoms; periodontal disease (PD) is an inflammatory oral disorder caused by immune-mediated damage against subgingival microflora. Although clinical evidence suggests a potential association between SLE and PD, their shared pathogenic mechanisms remain unclear. This study aims to explore common genetic markers in SLE and PD that hold diagnostic and therapeutic implications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Microarray datasets for systemic lupus erythematosus (SLE) and periodontal disease (PD) were obtained from the Gene Expression Omnibus (GEO) database. Module genes between the two diseases were screened using Weighted Gene Co-expression Network Analysis (WGCNA), and module genes overlapping between the significant correlation modules of GSE61635 and GSE16134 were identified. Functional enrichment analyses of genes within overlapping modules and their significantly correlated associated modules were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Overlapping module genes underwent differential expression analysis in GSE16134. A diagnostic model was constructed using the Random Forest (RF) machine learning technique under Receiver Operating Characteristic (ROC) curve assessment, which top 10 key genes were screened and analyzed for differential expression across three datasets (GSE61635, GSE10334, and GSE50772) to identify hub genes. Protein-protein interaction (PPI) network analysis was conducted to explore relationships between hub genes. CIBERSORT and Gene Set Variation Analysis (GSVA) were used to evaluate the correlation between shared hub genes and immune infiltration patterns as well as metabolic pathways. Finally, hub genes were validated using additional datasets, single-cell RNA sequencing (scRNA-seq) data, and immunohistochemistry (IHC) experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using WGCNA, we identified significant correlation modules and overlapping module genes, which were subjected to differential expression analysis in different datasets. Further, 4 hub genes were screened and successfully used to build a prognostic model. Those shared hub genes were associated with immunological and metabolic processes in peripheral blood. The additional datasets, scRNA-seq and IHC results verified that LY96 and TMEM140, possessing the promising diagnostic and therapeutic performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>LY96 andTMEM140 can be used as new diagnostic and therapeutic markers for SLE and PD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1614044","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T05:30:07Z","timestamp":1753162207000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The novel diagnostic markers for systemic lupus erythematosus and periodontal disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Xuedi","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocui","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongjun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30546-X","article-title":"Novel paradigms in systemic lupus erythematosus","volume":"393","author":"D\u00f6rner","year":"2019","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.1003-9406.2010.04.013","article-title":"Study on the relationship of the haplotypes of programmed cell death 1 gene and ultraviolet history with systemic lupus erythematosus","volume":"27","author":"Peng","year":"2010","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213512","article-title":"First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR)","volume":"77","author":"Pons-Estel","year":"2018","journal-title":"Ann Rheum Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1177\/0961203320938447","article-title":"Association between periodontitis and systemic lupus erythematosus: a meta-analysis","volume":"29","author":"Zhong","year":"2020","journal-title":"Lupus"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-013-2473-2","article-title":"Periodontitis treatment improves systemic lupus erythematosus response to immunosuppressive therapy","volume":"33","author":"Fabbri","year":"2014","journal-title":"Clin Rheumatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1080\/10408363.2021.1907298","article-title":"The potential impact of salivary peptides in periodontitis","volume":"58","author":"Hirtz","year":"2021","journal-title":"Crit Rev Clin Lab Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbre.2015.09.001","article-title":"Periodontitis and systemic lupus erythematosus","volume":"56","author":"Sete","year":"2016","journal-title":"Rev Bras Reumatol Engl Ed"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051x.2000.027004267.x","article-title":"Is there a relationship between rheumatoid arthritis and periodontal disease","volume":"27","author":"Mercado","year":"2000","journal-title":"J Clin Periodontol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.14080","article-title":"Alpha-ketoglutarate alleviates systemic lupus erythematosus-associated periodontitis in a novel murine model","volume":"52","author":"Mao","year":"2025","journal-title":"J Clin periodontology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12865-024-00634-y","article-title":"Immune-mediated inflammatory diseases and periodontal disease: a bidirectional two-sample mendelian randomization study","volume":"25","author":"Zhang","year":"2024","journal-title":"BMC Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12846","article-title":"Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd","volume":"7","author":"Wang","year":"2016","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19063245","article-title":"Effective macrosomia prediction using random forest algorithm","volume":"19","author":"Wang","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2024.2318210","article-title":"Comprehensive analysis of anoikis-related genes in diagnosis osteoarthritis: based on machine learning and single-cell RNA sequencing data","volume":"52","author":"Zhang","year":"2024","journal-title":"Artif Cells Nanomed Biotechnol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2024.2318210","article-title":"Placenta inflammation is closely associated with gestational diabetes mellitus","volume":"13","author":"Pan","year":"2021","journal-title":"Am J Transl Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102824","article-title":"Profiles of immune cell infiltration and immune-related genes in the tumor microenvironment of osteosarcoma","volume":"12","author":"Zhang","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.107238","article-title":"Development of a macrophages-related 4-gene signature and nomogram for the overall survival prediction of hepatocellular carcinoma based on WGCNA and LASSO algorithm","volume":"90","author":"Yang","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.998244","article-title":"Impact of the host response and osteoblast lineage cells on periodontal disease","volume":"13","author":"Zhou","year":"2022","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinf"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.1995.tb00030.x","article-title":"The immunopathology of chronic inflammatory periodontal disease","volume":"10","author":"Sosroseno","year":"1995","journal-title":"FEMS Immunol Med Microbiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106588","article-title":"Single-cell RNA sequencing highlights the roles of C1QB and NKG7 in the pancreatic islet immune microenvironment in type 1 diabetes mellitus","volume":"187","author":"Ji","year":"2023","journal-title":"Pharmacol Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218345","article-title":"Review of single-cell RNA sequencing in the heart","volume":"21","author":"Yamada","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa891","article-title":"Comparative toxicogenomics database (CTD): update 2021","volume":"49","author":"Davis","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa971","article-title":"PubChem in 2021: new data content and improved web interfaces","volume":"49","author":"Kim","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J Comput Chem"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/md20010029","article-title":"Structure-based pharmacophore modeling, virtual screening, molecular docking, ADMET, and molecular dynamics (MD) simulation of potential inhibitors of PD-L1 from the library of marine natural products","volume":"20","author":"Luo","year":"2021","journal-title":"Mar Drugs"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/biom12121764","article-title":"Boosting the full potential of pyMOL with structural biology plugins","volume":"12","author":"Rosignoli","year":"2022","journal-title":"Biomolecules"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10070218","article-title":"The osteoclast in bone metastasis: player and target","volume":"10","author":"Maurizi","year":"2018","journal-title":"Cancers (Basel)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1007\/s12016-015-8521-8","article-title":"A comprehensive review of immunoreceptor regulation of osteoclasts","volume":"51","author":"Humphrey","year":"2016","journal-title":"Clin Rev Allergy Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.641162","article-title":"Role of OSCAR signaling in osteoclastogenesis and bone disease","volume":"9","author":"Nedeva","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-70913-6","article-title":"Gene profiling of Epstein-Barr Virus and human endogenous retrovirus in peripheral blood mononuclear cells of SLE patients: immune response implications","volume":"14","author":"Lemus","year":"2024","journal-title":"Sci Rep"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket428","article-title":"The association of cytokines with disease activity and damage scores in systemic lupus erythematosus patients","volume":"53","author":"McCarthy","year":"2014","journal-title":"Rheumatol (Oxford)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12068","article-title":"The role of microparticles in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus","volume":"78","author":"Dye","year":"2013","journal-title":"Scand J Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-016-0170-2","article-title":"Potential role of DARC-chemokine interaction in the recruitment of osteoclast precursors in response to bacterial lipopolysaccharide challenge","volume":"99","author":"Alemi","year":"2016","journal-title":"Calcif Tissue Int"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/cells9092073","article-title":"Osteoblast-osteoclast communication and bone homeostasis","volume":"9","author":"Kim","year":"2020","journal-title":"Cells"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1188774","article-title":"MAPK8 and CAPN1 as potential biomarkers of intervertebral disc degeneration overlapping immune infiltration, autophagy, and ceRNA","volume":"14","author":"Zhang","year":"2023","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051x.2003.20016.x","article-title":"Polymorphism at position -174 of IL-6 gene is associated with susceptibility to chronic periodontitis in a Caucasian Brazilian population","volume":"30","author":"Trevilatto","year":"2003","journal-title":"J Clin Periodontol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2011.01437.x","article-title":"Genetic polymorphism studies in periodontitis and Fc\u03b3 receptors","volume":"47","author":"Chai","year":"2012","journal-title":"J Periodontal Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02602","article-title":"Host-microbial interactions in systemic lupus erythematosus and periodontitis","volume":"10","author":"Pessoa","year":"2019","journal-title":"Front Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2004.058065","article-title":"Dental disease in children with chronic illness","volume":"90","author":"Foster","year":"2005","journal-title":"Arch Dis Child"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1998.69.8.865","article-title":"The relationship between concentrations of proinflammatory cytokines within gingiva and the adjacent sulcular depth","volume":"69","author":"McGee","year":"1998","journal-title":"J Periodontol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-018-4124-0","article-title":"Aberrant T cell subsets and cytokines expression profile in systemic lupus erythematosus","volume":"37","author":"Zhou","year":"2018","journal-title":"Clin Rheumatol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1111\/j.1834-7819.2009.01139.x","article-title":"The immunopathogenesis of periodontal disease","author":"Ohlrich","year":"2009","journal-title":"Aust Dent J"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1614044\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T05:30:09Z","timestamp":1753162209000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1614044\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,22]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2025.1614044"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1614044","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,22]]},"article-number":"1614044"}}