{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T13:57:04Z","timestamp":1772632624344,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"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>The pathogenesis of systemic lupus erythematosus (SLE) is closely associated with abnormal activation of B lymphocytes. Telitacicept simultaneously blocks B-cell stimulating factors and proliferation-inducing ligands, thereby inhibiting B-cell proliferation and differentiation, demonstrating favorable therapeutic efficacy in the majority of SLE patients. However, there is a lack of reliable biomarkers of efficacy and systematic elucidation of its mechanism of action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The study employed proteomics and metabolomics analysis to explore biomarkers and mechanisms underlying therapeutic response variability to Telitacicept in SLE patients. Twenty-five SLE patients were enrolled and divided into the responder group and non-responder group based on the SLE Response Index 4 to identify key proteins, metabolites, and mechanisms associated with treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Proteomics results revealed XPNPEP3, SRSF5, SRSF6, WARS1, IDH1, and ITLN1 as protein biomarkers correlated with Telitacicept efficacy in SLE patients. Metabolomics results indicated that pyruvate was a potential metabolic biomarker for responder group, while gamma-aminobutyric acid (GABA) was a potential biomarker for non-responder group. The combined analysis revealed that both pyruvate and IDH1 participate in the citric acid cycle. GABA showed a negative correlation with XPNPEP3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The above results reveal biomarkers related to the differential efficacy of Telitacicept in treating SLE patients and potential mechanisms underlying these differences, which may provide a reference for personalized treatment and mechanistic research in SLE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1779880","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:03:24Z","timestamp":1772607804000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling biomarkers of telitacicept\u2019s efficacy in SLE treatment through proteomics and metabolomics"],"prefix":"10.3389","volume":"17","author":[{"given":"Huiyu","family":"Nie","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanhan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahui","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofei","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Second Xiangya Hospital of Central South University","place":["Changsha, Hunan, China"]},{"name":"Clinical Medical Research Center for Systemic Autoimmune Diseases","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"Itc81","DOI":"10.7326\/aitc202006020","article-title":"Systemic lupus erythematosus","volume":"172","author":"Kiriakidou","year":"2020","journal-title":"Ann Intern Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223035","article-title":"Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study","volume":"82","author":"Tian","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1080\/08916934.2019.1700232","article-title":"The pathological role of B cells in systemic lupus erythematosus: From basic research to clinical","volume":"53","author":"Feng","year":"2020","journal-title":"Autoimmunity"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102736","article-title":"B cell activating factor (BAFF): Structure, functions, autoimmunity and clinical implications in Systemic Lupus Erythematosus (SLE)","volume":"20","author":"M\u00f6ckel","year":"2021","journal-title":"Autoimmun Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1093208","article-title":"Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus","volume":"14","author":"Wen","year":"2023","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.33","article-title":"The BAFF\/APRIL system in SLE pathogenesis","volume":"10","author":"Vincent","year":"2014","journal-title":"Nat Rev Rheumatol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead696","article-title":"Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients","volume":"64","author":"Altab\u00e1s-Gonz\u00e1lez","year":"2025","journal-title":"Rheumatol (Oxford)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185x.12463","article-title":"Current role of rituximab in systemic lupus erythematosus","volume":"18","author":"Mok","year":"2015","journal-title":"Int J Rheum Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224854","article-title":"Telitacicept in patients with active systemic lupus erythematosus: results of a phase 2b, randomised, double-blind, placebo-controlled trial","volume":"83","author":"Wu","year":"2024","journal-title":"Ann Rheum Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01591-1","article-title":"Telitacicept: first approval","volume":"81","author":"Dhillon","year":"2021","journal-title":"Drugs"},{"key":"B11","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1177\/09612033221141253","article-title":"The efficacy and safety of telitacicept for the treatment of systemic lupus erythematosus: a real life observational study","volume":"32","author":"Chen","year":"2023","journal-title":"Lupus"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-025-07348-5","article-title":"Effectiveness and safety of telitacicept in patients with systemic lupus erythematosus: a single center, retrospective, real-world study","volume":"44","author":"Fang","year":"2025","journal-title":"Clin Rheumatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2013.3","article-title":"The applied basic research of systemic lupus erythematosus based on the biological omics","volume":"14","author":"Sui","year":"2013","journal-title":"Genes Immun"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1002\/art.1780400928","article-title":"Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus","volume":"40","author":"Hochberg","year":"1997","journal-title":"Arthritis Rheumatol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39339.610000.BE","article-title":"The declaration of Helsinki","volume":"335","author":"Goodyear","year":"2007","journal-title":"BMJ"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2011.06.011","article-title":"The Systemic Lupus Erythematosus Responder Index (SRI); a new SLE disease activity assessment","volume":"11","author":"Luijten","year":"2012","journal-title":"Autoimmun Rev"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-199409000-00006","article-title":"Indicators of disease activity, prognosis, and treatment of systemic lupus erythematosus","volume":"6","author":"Gladman","year":"1994","journal-title":"Curr Opin Rheumatol"},{"key":"B18","article-title":"The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus","volume":"86","author":"Hay","year":"1993","journal-title":"Q J Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa383","article-title":"Use of Physician Global Assessment in systemic lupus erythematosus: a systematic review of its psychometric properties","volume":"59","author":"Chessa","year":"2020","journal-title":"Rheumatol (Oxford)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1017\/s0033583597003399","article-title":"Protein identification in the post-genome era: the rapid rise of proteomics","volume":"30","author":"James","year":"1997","journal-title":"Q Rev Biophys"},{"key":"B21","doi-asserted-by":"publisher","first-page":"7155","DOI":"10.3390\/jcm11237155","article-title":"The plasma DIA-based quantitative proteomics reveals the pathogenic pathways and new biomarkers in cervical cancer and high grade squamous intraepithelial lesion","volume":"11","author":"Han","year":"2022","journal-title":"J Clin Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0339558","article-title":"Identification of diagnostic and prognostic biomarkers for tuberculosis based on plasma proteomics","volume":"20","author":"Hu","year":"2025","journal-title":"PLoS One"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2147\/ccid.S556629","article-title":"Metabolomic profiling reveals distinct plasma metabolic signatures in acne patients with and without depression","volume":"18","author":"Chen","year":"2025","journal-title":"Clin Cosmet Investig Dermatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1546665","article-title":"Analysis of serum amino acids and tryptophan metabolites to predict hepatic encephalopathy in portal hypertension patients receiving a transjugular intrahepatic portal shunt (TIPS)","volume":"16","author":"Bao","year":"2025","journal-title":"Front Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22531","article-title":"XPNPEP3 is a novel transcriptional target of canonical Wnt\/\u03b2-catenin signaling","volume":"57","author":"Kumar","year":"2018","journal-title":"Genes Chromosomes Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202203088","article-title":"SRSF5-mediated alternative splicing of M gene is essential for influenza A virus replication: A host-directed target against influenza virus","volume":"9","author":"Li","year":"2022","journal-title":"Adv Sci (Weinh)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-023-00790-3","article-title":"Identification of Key lncRNAs, circRNAs, and mRNAs in Osteoarthritis via Bioinformatics Analysis","volume":"66","author":"Zhang","year":"2024","journal-title":"Mol Biotechnol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/mpgq0y","article-title":"A candidate gene study reveals association between a variant of the SRp55 splicing factor gene and systemic sclerosis","volume":"40","author":"Romano","year":"2022","journal-title":"Clin Exp Rheumatol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2300752","article-title":"Single-cell RNA sequencing identifies WARS1+ Mesenchymal stem cells with enhanced immunomodulatory capacity and improved therapeutic efficacy","volume":"213","author":"Li","year":"2024","journal-title":"J Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.01.005","article-title":"Metabolic dysregulation of lymphocytes in autoimmune diseases","volume":"35","author":"Wang","year":"2024","journal-title":"Trends Endocrinol Metab"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.114205","article-title":"Omentin-1 modulates interleukin expression and macrophage polarization: Implications for rheumatoid arthritis therapy","volume":"149","author":"Lin","year":"2025","journal-title":"Int Immunopharmacol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1477708","article-title":"Roles of macrophages in lupus nephritis","volume":"15","author":"Cheng","year":"2024","journal-title":"Front Pharmacol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-019-00668-4","article-title":"Analysis of brain metabolites by gas chromatography-mass spectrometry reveals the risk-benefit concerns of prednisone in MRL\/lpr lupus mice","volume":"28","author":"Zhou","year":"2020","journal-title":"Inflammopharmacology"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/602154","article-title":"The association of the GABRP polymorphisms with systemic lupus erythematosus","volume":"2015","author":"Kim","year":"2015","journal-title":"J Immunol Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket481","article-title":"Identification of novel autoantibodies to GABA(B) receptors in patients with neuropsychiatric systemic lupus erythematosus","volume":"53","author":"Tsuchiya","year":"2014","journal-title":"Rheumatol (Oxford)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key282","article-title":"Association of antibodies against myelin and neuronal antigens with neuroinflammation in systemic lupus erythematosus","volume":"58","author":"Pr\u00f6bstel","year":"2019","journal-title":"Rheumatol (Oxford)"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02088-5","article-title":"In defence of ferroptosis","volume":"10","author":"Alves","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00493","article-title":"IDH1: linking metabolism and epigenetics","volume":"9","author":"Raineri","year":"2018","journal-title":"Front Genet"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2017.06.002","article-title":"Oncogenic activities of IDH1\/2 mutations: from epigenetics to cellular signaling","volume":"27","author":"Gagn\u00e9","year":"2017","journal-title":"Trends Cell Biol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e20221085","DOI":"10.1084\/jem.20221085","article-title":"Chronic activation of pDCs in autoimmunity is linked to dysregulated ER stress and metabolic responses","volume":"219","author":"Chaudhary","year":"2022","journal-title":"J Exp Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110912","article-title":"Mitochondrial respiration in B lymphocytes is essential for humoral immunity by controlling the flux of the TCA cycle","volume":"39","author":"Urbanczyk","year":"2022","journal-title":"Cell Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1779880\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T07:03:25Z","timestamp":1772607805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1779880\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":42,"alternative-id":["10.3389\/fimmu.2026.1779880"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1779880","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"article-number":"1779880"}}