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The pathogenic mechanisms are not fully understood. Integrated transcriptomic analysis could provide insights into monitoring tuberculosis progression after TNFi therapy and help reduce LTBI reactivation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We selected six transcriptomic datasets from studies related to TNFi treatment and tuberculosis. Pathway enrichment, pseudotime, and transcription factor analyses were performed to explore the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our analysis revealed distinct transcriptional changes in memory B cells during tuberculosis progression and TNFi therapy. In active tuberculosis (ATB), ROR1\n                      <jats:sup>+<\/jats:sup>\n                      memory B cells were identified in a noncanonical differentiation trajectory, characterized by downregulation of B cell\u2010related genes (e.g., CD22, EBF1, MS4A1), reduced translational capacity, and suppression of immune response pathways, accompanied by upregulation of oxidative phosphorylation, which highlighted metabolic alterations during tuberculosis progression. A similar subtype also emerged in TNFi\u2010treated patients, suggesting that metabolic reprogramming of memory B cells may disrupt immune balance, thereby contributing to LTBI reactivation and ATB development following TNFi therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study integrates bioinformatics and single\u2010cell RNA sequencing to reveal the role of memory B cells in ATB progression and TNFi treatment, offering insights into TNFi\u2010associated TB susceptibility and potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1756-185x.70311","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:41:29Z","timestamp":1753094489000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Noncanonical Differentiation of Memory B Cells Drives Latent Tuberculosis Infection Reactivation Upon Tumor Necrosis Factor\u2010Alpha Inhibitor Therapy: An Integrative Transcriptomic Study"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6517-9510","authenticated-orcid":false,"given":"Xinyu","family":"Yu","sequence":"first","affiliation":[{"name":"Rheumatology and Immunology Department Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Department Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0520-0688","authenticated-orcid":false,"given":"Xiqing","family":"Luo","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Department Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9953-1315","authenticated-orcid":false,"given":"Xianghui","family":"Wen","sequence":"additional","affiliation":[{"name":"Shenzhen Longhua Institute of Immunology Transformation  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zena","family":"Chen","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Department Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shude","family":"Chen","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Department Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Budian","family":"Liu","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Department Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0592-1043","authenticated-orcid":false,"given":"Jinwei","family":"Li","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Department Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Department Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieruo","family":"Gu","sequence":"additional","affiliation":[{"name":"Rheumatology and Immunology Department Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.19\u20102\u2010s117"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i25.2764"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-017-3916-y"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2666\u20105247(22)00359\u20107"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.943545"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11111228"},{"issue":"6","key":"e_1_2_11_8_1","article-title":"The Performance and Limitation of T\u2010SPOT. 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