{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T10:17:43Z","timestamp":1788171463467,"version":"build-2803163510"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) patients have a clearly increased possibility to develop tuberculosis (TB). However, the common molecular background, useful diagnostic molecules, and treatment-related targets of this comorbidity are still not sufficiently explained. We attempted to search the shared genetic factors and candidate drug targets for RA and TB by an integrated multi-omics way.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bulk transcriptome data sets for RA and TB were obtained from Gene Expression Omnibus (GEO). Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were first performed to collect overlapped disease-related genes. Least Absolute Shrinkage and Selection Operator (LASSO) regression was then applied to select hub genes. External data sets, single-cell RNA sequencing (scRNA-seq), and quantitative real-time PCR (qRT-PCR) using clinical samples were used for validation. We also carried out immune infiltration analysis, gene set enrichment analyses, molecular docking, and 100 ns molecular dynamics (MD) simulation, in order to describe possible function and treatment value of these genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 312 co-expressed genes common to RA and TB were obtained, and these genes were mainly gathered in immune and inflammatory processes.\n                      <jats:italic>MARCO<\/jats:italic>\n                      and\n                      <jats:italic>ZBTB20<\/jats:italic>\n                      were kept as hub genes and showed acceptable diagnostic ability in RA (AUC\u00a0=\u00a00.839 and 0.795, respectively) and TB (AUC\u00a0=\u00a00.849 and 0.915, respectively). Single-cell results suggested their expression in T cells, B cells, and myeloid cell lineages, tightly correlated with immune infiltration and inflammatory signaling. Computational drug-repurposing analysis identified Tipifarnib as a candidate compound, and molecular docking and molecular dynamics simulations predicted potentially stable interactions with\n                      <jats:italic>MARCO<\/jats:italic>\n                      and\n                      <jats:italic>ZBTB20<\/jats:italic>\n                      . In the clinical cohort,\n                      <jats:italic>MARCO<\/jats:italic>\n                      expression was significantly higher in the RA-TB group than in healthy controls, whereas\n                      <jats:italic>ZBTB20<\/jats:italic>\n                      did not differ significantly among the four groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study suggests that\n                      <jats:italic>MARCO<\/jats:italic>\n                      and\n                      <jats:italic>ZBTB20<\/jats:italic>\n                      may act as common diagnostic biomarkers for RA and TB. The clinical findings provide preliminary support for\n                      <jats:italic>MARCO<\/jats:italic>\n                      as a marker associated with RA\u2013TB comorbidity, whereas the translational relevance of\n                      <jats:italic>ZBTB20<\/jats:italic>\n                      requires further validation. These findings provide a molecular framework for further investigation of RA\u2013TB comorbidity and may inform the future development of tissue-specific biomarkers and targeted interventions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1886037","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:47:58Z","timestamp":1788169678000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated multi-omics analysis indicates MARCO and ZBTB20 as candidate biomarkers in rheumatoid arthritis and tuberculosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Weihua","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Shenzhen Third People\u2019s Hospital","place":["Shenzhen, China"]},{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, Southern University of Science and Technology","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shenzhen Third People\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keli","family":"He","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shenzhen Third People\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shenzhen Third People\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cantong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shenzhen Third People\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifang","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Shenzhen Third People\u2019s Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.13103","article-title":"Diagnosis and management of rheumatoid arthritis: a review","volume":"320","author":"Aletaha","year":"2018","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200627","article-title":"Genetic predisposition of the severity of joint destruction in rheumatoid arthritis: a population-based study","volume":"71","author":"Knevel","year":"2012","journal-title":"Ann Rheum Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nature12873","article-title":"Genetics of rheumatoid arthritis contributes to biology and drug discovery","volume":"506","author":"Okada","year":"2014","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.120170","article-title":"Cumulative association of 22 genetic variants with seropositive rheumatoid arthritis risk","volume":"69","author":"Karlson","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/8909834","article-title":"Risk of tuberculosis reactivation in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis receiving non-anti-TNF-targeted biologics","volume":"2017","author":"Cantini","year":"2017","journal-title":"Mediators Inflammation"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(22)00359-7","article-title":"WHO's global tuberculosis report 2022","volume":"4","author":"Bagcchi","year":"2023","journal-title":"Lancet Microbe"},{"key":"B7","unstructured":"Tuberculosis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-020-04583-8","article-title":"A retrospective study on the risk of tuberculosis in patients with rheumatoid arthritis","volume":"40","author":"Chung","year":"2020","journal-title":"Rheumatol Int"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204960","article-title":"Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments","volume":"74","author":"Arkema","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/iub.2413","article-title":"Tuberculosis comorbidity with rheumatoid arthritis: gene signatures, associated biomarkers, and screening","volume":"73","author":"Zafari","year":"2021","journal-title":"IUBMB Life"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000001948","article-title":"Risk of tuberculosis in patients with rheumatoid arthritis treated with biological and targeted drugs: meta-analysis of randomized clinical trials","volume":"135","author":"Ji","year":"2022","journal-title":"Chin Med J (Engl)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinf"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btae615","article-title":"DAVID ortholog: an integrative tool to enhance functional analysis through orthologs","volume":"40","author":"Sherman","year":"2024","journal-title":"Bioinformatics"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw1092","article-title":"KEGG: new perspectives on genomes, pathways, diseases and drugs","volume":"45","author":"Kanehisa","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s13148-019-0730-1","article-title":"Statistical predictions with glmnet","volume":"11","author":"Engebretsen","year":"2019","journal-title":"Clin Epigenet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2022.997713","article-title":"From past to future: bibliometric analysis of global research productivity on nomogram (2000-2021)","volume":"10","author":"Wang","year":"2022","journal-title":"Front Public Health"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat Methods"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1187","article-title":"Gene set correlation enrichment analysis for interpreting and annotating gene expression profiles","volume":"52","author":"Chang","year":"2024","journal-title":"Nucleic Acids Res"},{"key":"B19","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":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.08.034","article-title":"MicroRNA","volume":"141","author":"Lu","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/s41392-024-01888-z","article-title":"Cell-cell communication: new insights and clinical implications","volume":"9","author":"Su","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2020.105745","article-title":"Inclusion of temporal information in single cell transcriptomics","volume":"122","author":"Olivares-Chauvet","year":"2020","journal-title":"Int J Biochem Cell Biol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbw112","article-title":"A review of connectivity map and computational approaches in pharmacogenomics","volume":"19","author":"Musa","year":"2018","journal-title":"Brief Bioinform"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2022.102503","article-title":"Integrating experimental data with molecular simulations to investigate RNA structural dynamics","volume":"78","author":"Bernetti","year":"2023","journal-title":"Curr Opin Struct Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3201\/eid2108.141846","article-title":"Risk for mycobacterial disease among patients with rheumatoid arthritis, Taiwan, 2001-2011","volume":"21","author":"Liao","year":"2015","journal-title":"Emerg Infect Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1080\/23744235.2019.1682187","article-title":"High risk of activation of latent tuberculosis infection in rheumatic disease patients","volume":"52","author":"Long","year":"2020","journal-title":"Infect Dis (Lond)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/s13075-023-03111-w","article-title":"Comparative risk of infections between JAK inhibitors versus TNF inhibitors among patients with rheumatoid arthritis: a cohort study","volume":"25","author":"Choi","year":"2023","journal-title":"Arthritis Res Ther"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.4110\/in.2024.24.e4","article-title":"TNF in human tuberculosis: a double-edged sword","volume":"24","author":"Yuk","year":"2024","journal-title":"Immune Netw"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.201251","article-title":"Tuberculosis in biologic-na\u00efve patients with rheumatoid arthritis: risk factors and tuberculosis characteristics","volume":"48","author":"Sundbaum","year":"2021","journal-title":"Rheumatol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s13075-022-02842-6","article-title":"Comparison of developing tuberculosis following tumor necrosis factor inhibition and interleukin-6 inhibition in patients with rheumatoid arthritis: a nationwide observational study in South Korea, 2013-2018","volume":"24","author":"Jung","year":"2022","journal-title":"Arthritis Res Ther"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.151037","article-title":"PLG nanoparticles target fibroblasts and MARCO+ monocytes to reverse multiorgan fibrosis","volume":"7","author":"Xu","year":"2022","journal-title":"JCI Insight"},{"key":"B32","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1007\/s00018-025-05707-8","article-title":"Single-cell multi-dimensional data analysis decodes RNF19A-mediated drug resistance in rheumatoid arthritis fibroblast-like synoviocytes: mechanisms and biological insights","volume":"82","author":"Luo","year":"2025","journal-title":"Cell Mol Life Sci"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204494200","article-title":"Characterization of recombinant soluble macrophage scavenger receptor MARCO","volume":"277","author":"Sankala","year":"2002","journal-title":"J Biol Chem"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700057","article-title":"Scavenger receptor MARCO orchestrates early defenses and contributes to fungal containment during cryptococcal infection","volume":"198","author":"Xu","year":"2017","journal-title":"J Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-20-1885","article-title":"Targeting MARCO and IL37R on immunosuppressive macrophages in lung cancer blocks regulatory T cells and supports cytotoxic lymphocyte function","volume":"81","author":"La Fleur","year":"2021","journal-title":"Cancer Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.toxlet.2018.10.031","article-title":"Inhibition of MARCO ameliorates silica-induced pulmonary fibrosis by regulating epithelial-mesenchymal transition","volume":"301","author":"Yang","year":"2019","journal-title":"Toxicol Lett"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00670-17","article-title":"Key role of the scavenger receptor MARCO in mediating adenovirus infection and subsequent innate responses of macrophages","volume":"8","author":"Maler","year":"2017","journal-title":"mBio"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000474","article-title":"MARCO, TLR2, and CD14 are required for macrophage cytokine responses to mycobacterial trehalose dimycolate and Mycobacterium tuberculosis","volume":"5","author":"Bowdish","year":"2009","journal-title":"PloS Pathog"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.17599","article-title":"Polyguanine alleviated autoimmune hepatitis through regulation of macrophage receptor with collagenous structure and TLR4-TRIF-NF-\u03baB signalling","volume":"26","author":"Cai","year":"2022","journal-title":"J Cell Mol Med"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-016-2035-x","article-title":"Regulation of hematopoietic development by ZBTB transcription factors","volume":"104","author":"Maeda","year":"2016","journal-title":"Int J Hematol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.4689","article-title":"Identification and characterization of DPZF, a novel human BTB\/POZ zinc finger protein sharing homology to BCL-6","volume":"282","author":"Zhang","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22035","article-title":"Regulation of archicortical arealization by the transcription factor Zbtb20","volume":"22","author":"Rosenthal","year":"2012","journal-title":"Hippocampus"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1053\/j.gastro.2012.02.043","article-title":"The zinc finger protein ZBTB20 regulates transcription of fructose-1,6-bisphosphatase 1 and \u03b2 cell function in mice","volume":"142","author":"Zhang","year":"2012","journal-title":"Gastroenterology"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1301257110","article-title":"Zinc finger protein ZBTB20 promotes Toll-like receptor-triggered innate immune responses by repressing I\u03baB\u03b1 gene transcription","volume":"110","author":"Liu","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000459","article-title":"Zbtb-20 restrains CD8 T cell immunometabolism and restricts memory differentiation and antitumor immunity","volume":"205","author":"Sun","year":"2020","journal-title":"J Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1007624","article-title":"Potential diagnostic markers and therapeutic targets for rheumatoid arthritis with comorbid depression based on bioinformatics analysis","volume":"14","author":"Zhou","year":"2023","journal-title":"Front Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/biom14020192","article-title":"Zinc finger and BTB domain-containing 20: a newly emerging player in pathogenesis and development of human cancers","volume":"14","author":"Liu","year":"2024","journal-title":"Biomolecules"},{"key":"B48","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/s1470-2045(00)00191-1","article-title":"Farnesyl transferase inhibitors: a novel targeted tnerapy for cancer","volume":"2","author":"Johnston","year":"2001","journal-title":"Lancet Oncol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.10-8-565","article-title":"Development of farnesyl transferase inhibitors: a review","volume":"10","author":"Appels","year":"2005","journal-title":"Oncologist"},{"key":"B50","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1124\/jpet.105.095976","article-title":"Anti-inflammatory activity in vitro and in vivo of the protein farnesyltransferase inhibitor tipifarnib","volume":"317","author":"Xue","year":"2006","journal-title":"J Pharmacol Exp Ther"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1886037\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:48:00Z","timestamp":1788169680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1886037\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":50,"alternative-id":["10.3389\/fimmu.2026.1886037"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1886037","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"article-number":"1886037"}}