{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T03:47:36Z","timestamp":1768794456431,"version":"3.49.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100014937","name":"Cerecor","doi-asserted-by":"publisher","award":["SPF"],"award-info":[{"award-number":["SPF"]}],"id":[{"id":"10.13039\/100014937","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006458","name":"Children\u2019s Hospital of Philadelphia","doi-asserted-by":"publisher","award":["IDF"],"award-info":[{"award-number":["IDF"]}],"id":[{"id":"10.13039\/100006458","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes), encoded by the TNFSF14 gene, is a cytokine belonging to the TNF superfamily. On binding to its receptors, herpes virus entry mediator and lymphotoxin \u03b2 receptor, it activates inflammatory responses. We conducted this study to determine whether plasma LIGHT levels are elevated in Crohn\u2019s disease (CD) in a pediatric population with the aim of nominating this cytokine as a therapeutic target. We used a single-molecule immunoassay to determine the circulating levels of free LIGHT in plasma from pediatric patients with CD in our biobank (n = 183), a panel of healthy pediatric (n = 9) or adult (n = 22) reference samples, and pediatric biobank controls (n = 19). We performed correlational analyses between LIGHT levels and the clinical characteristics of the CD cohort, including age, Montreal classification, family history, medical\/surgical therapy, and routine blood test parameters. LIGHT levels were greatly elevated in CD, with an average of 305 versus 32.4 pg\/ml for controls from the biobank (p &amp;lt; 0.0001). The outside reference samples showed levels of 57 pg\/ml in pediatric controls and 55 pg\/ml in adults (p &amp;lt; 0.0001). We found a statistically significant correlation between white blood cell count and free LIGHT (p &amp;lt; 0.046). We conclude that free, soluble LIGHT is increased 5- to 10-fold in pediatric CD across an array of disease subtypes and characteristics.<\/jats:p>","DOI":"10.4049\/jimmunol.2200652","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T13:52:20Z","timestamp":1674481940000},"page":"590-594","source":"Crossref","is-referenced-by-count":3,"title":["Elevated Levels of the Cytokine LIGHT in Pediatric Crohn\u2019s Disease"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7513-8977","authenticated-orcid":false,"given":"Christopher J","family":"Cardinale","sequence":"first","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debra J","family":"Abrams","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4889-6961","authenticated-orcid":false,"given":"Frank D","family":"Mentch","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A","family":"Cardinale","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlly","family":"Kao","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick M A","family":"Sleiman","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA"},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-7461","authenticated-orcid":false,"given":"Hakon","family":"Hakonarson","sequence":"additional","affiliation":[{"name":"Center for Applied Genomics, Children\u2019s Hospital of Philadelphia , Philadelphia, PA"},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"2025021008001876700_r1","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1146\/annurev-immunol-030409-101225","article-title":"Inflammatory bowel disease","volume":"28","author":"Kaser","year":"2010","journal-title":"Annu. Rev. Immunol."},{"key":"2025021008001876700_r2","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1093\/hmg\/ddq078","article-title":"Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects","volume":"19","author":"Wang","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"2025021008001876700_r3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S1074-7613(00)80455-0","article-title":"LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator","volume":"8","author":"Mauri","year":"1998","journal-title":"Immunity"},{"key":"2025021008001876700_r4","doi-asserted-by":"crossref","first-page":"4105","DOI":"10.4049\/jimmunol.164.8.4105","article-title":"LIGHT, a TNF-like molecule, costimulates T cell proliferation and is required for dendritic cell-mediated allogeneic T cell response","volume":"164","author":"Tamada","year":"2000","journal-title":"J. Immunol."},{"key":"2025021008001876700_r5","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/25387","article-title":"Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer","volume":"396","author":"Pitti","year":"1998","journal-title":"Nature"},{"key":"2025021008001876700_r6","doi-asserted-by":"crossref","first-page":"eaax9198","DOI":"10.1126\/science.aax9198","article-title":"A genome-wide transcriptomic analysis of protein-coding genes in human blood cells","volume":"366","author":"Uhlen","year":"2019","journal-title":"Science"},{"key":"2025021008001876700_r7","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S0898-6568(01)00160-7","article-title":"The TNF-receptor-associated factor family: scaffold molecules for cytokine receptors, kinases and their regulators","volume":"13","author":"Wajant","year":"2001","journal-title":"Cell. Signal."},{"key":"2025021008001876700_r8","doi-asserted-by":"crossref","first-page":"a016279","DOI":"10.1101\/cshperspect.a016279","article-title":"Tumor necrosis factor superfamily in innate immunity and inflammation","volume":"7","author":"\u0160ed\u00fd","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2025021008001876700_r9","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/ng.3359","article-title":"Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations","volume":"47","author":"Liu","year":"2015","journal-title":"Nat. Genet."},{"key":"2025021008001876700_r10","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/ng.3760","article-title":"Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease","volume":"49","author":"de Lange","year":"2017","journal-title":"Nat. Genet."},{"key":"2025021008001876700_r11","doi-asserted-by":"crossref","first-page":"eaav7188","DOI":"10.1126\/science.aav7188","article-title":"Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility","volume":"365","author":"International Multiple Sclerosis Genetics Consortium","year":"2019","journal-title":"Science"},{"key":"2025021008001876700_r12","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/apt.16136","article-title":"Machine learning identifies novel blood protein predictors of penetrating and stricturing complications in newly diagnosed paediatric Crohn\u2019s disease","volume":"53","author":"Ungaro","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"2025021008001876700_r13","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/ibd\/izz322","article-title":"Systemic inflammatory protein profiles distinguish irritable bowel syndrome (IBS) and ulcerative colitis, irrespective of inflammation or IBS-like symptoms","volume":"26","author":"Moraes","year":"2020","journal-title":"Inflamm. Bowel Dis."},{"key":"2025021008001876700_r14","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1093\/ecco-jcc\/jjz072","article-title":"Mucosal and systemic immune profiles differ during early and late phases of the disease in patients with active ulcerative colitis","volume":"13","author":"Mavroudis","year":"2019","journal-title":"J. Crohn\u2019s Colitis"},{"key":"2025021008001876700_r15","doi-asserted-by":"crossref","first-page":"e0186142","DOI":"10.1371\/journal.pone.0186142","article-title":"Subphenotypes of inflammatory bowel disease are characterized by specific serum protein profiles","volume":"12","author":"Andersson","year":"2017","journal-title":"PLoS One"},{"key":"2025021008001876700_r16","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1002\/ibd.21493","article-title":"Pediatric modification of the Montreal classification for inflammatory bowel disease: the Paris classification","volume":"17","author":"Levine","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"2025021008001876700_r17","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3390\/biomedicines10020264","article-title":"Circulating LIGHT (TNFSF14) and interleukin-18 levels in sepsis-induced multi-organ injuries","volume":"10","author":"Qu","year":"2022","journal-title":"Biomedicines"},{"key":"2025021008001876700_r18","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1164\/rccm.200703-506OC","article-title":"Raised LIGHT levels in pulmonary arterial hypertension: potential role in thrombus formation","volume":"177","author":"Otterdal","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2025021008001876700_r19","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1007\/s13258-020-00974-0","article-title":"The impact of TNFSF14 on prognosis and immune microenvironment in clear cell renal cell carcinoma","volume":"42","author":"Xu","year":"2020","journal-title":"Genes Genomics"},{"key":"2025021008001876700_r20","doi-asserted-by":"crossref","first-page":"614781","DOI":"10.3389\/fimmu.2020.614781","article-title":"Plasma TNFSF13B and TNFSF14 function as inflammatory indicators of severe adenovirus pneumonia in pediatric patients","volume":"11","author":"Fan","year":"2021","journal-title":"Front. Immunol."},{"key":"2025021008001876700_r21","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1111\/ane.13394","article-title":"Increased level of LIGHT\/TNFSF14 is associated with survival in aneurysmal subarachnoid hemorrhage","volume":"143","author":"Schranz","year":"2021","journal-title":"Acta Neurol. Scand."},{"key":"2025021008001876700_r22","doi-asserted-by":"crossref","first-page":"7112","DOI":"10.18632\/aging.103065","article-title":"Identification of immunologic subtype and prognosis of GBM based on TNFSF14 and immune checkpoint gene expression profiling","volume":"12","author":"Long","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"2025021008001876700_r23","doi-asserted-by":"crossref","first-page":"4739","DOI":"10.3390\/ijms21134739","article-title":"Shedding \u201cLIGHT\u201d on the link between bone and fat in obese children and adolescents","volume":"21","author":"Brunetti","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2025021008001876700_r24","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.3389\/fimmu.2019.02939","article-title":"Neonatal antibiotic treatment is associated with an altered circulating immune marker profile at 1 year of age","volume":"10","author":"Oosterloo","year":"2020","journal-title":"Front. Immunol."},{"key":"2025021008001876700_r25","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1161\/ATVBAHA.118.312166","article-title":"Circulating TNFSF14 (tumor necrosis factor superfamily 14) predicts clinical outcome in patients with stable coronary artery disease","volume":"39","author":"Hsu","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"2025021008001876700_r26","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.3389\/fimmu.2018.02459","article-title":"LIGHT\/TNFSF14 as a new biomarker of bone disease in multiple myeloma patients experiencing therapeutic regimens","volume":"9","author":"Brunetti","year":"2018","journal-title":"Front. Immunol."},{"key":"2025021008001876700_r27","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.preghy.2018.10.004","article-title":"Serum soluble LIGHT in the early third trimester as a novel biomarker for predicting late-onset preeclampsia","volume":"14","author":"Hirashima","year":"2018","journal-title":"Pregnancy Hypertens."},{"key":"2025021008001876700_r28","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.phrs.2005.03.009","article-title":"Lymphtoxin beta receptor-Ig ameliorates TNBS-induced colitis via blocking LIGHT\/HVEM signaling","volume":"52","author":"An","year":"2005","journal-title":"Pharmacol. Res."},{"key":"2025021008001876700_r29","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/j.1365-2567.2009.03131.x","article-title":"Neutralization of LIGHT ameliorates acute dextran sodium sulphate-induced intestinal inflammation","volume":"128","author":"Jungbeck","year":"2009","journal-title":"Immunology"},{"key":"2025021008001876700_r30","doi-asserted-by":"crossref","first-page":"8173","DOI":"10.4049\/jimmunol.174.12.8173","article-title":"The critical role of LIGHT in promoting intestinal inflammation and Crohn\u2019s disease","volume":"174","author":"Wang","year":"2005","journal-title":"J. Immunol."},{"key":"2025021008001876700_r31","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.3389\/fimmu.2018.02585","article-title":"The tumor necrosis factor superfamily members TNFSF14 (LIGHT), lymphotoxin \u03b2 and lymphotoxin \u03b2 receptor interact to regulate intestinal inflammation","volume":"9","author":"Giles","year":"2018","journal-title":"Front. Immunol."},{"key":"2025021008001876700_r32","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1053\/j.gastro.2014.02.010","article-title":"The tumor necrosis factor family member TNFSF14 (LIGHT) is required for resolution of intestinal inflammation in mice","volume":"146","author":"Krause","year":"2014","journal-title":"Gastroenterology"},{"key":"2025021008001876700_r33","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.cell.2018.08.067","article-title":"Structural remodeling of the human colonic mesenchyme in inflammatory bowel disease","volume":"175","author":"Kinchen","year":"2018","journal-title":"Cell"},{"key":"2025021008001876700_r34","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1084\/jem.20170536","article-title":"LIGHT-HVEM signaling in keratinocytes controls development of dermatitis","volume":"215","author":"Herro","year":"2018","journal-title":"J. Exp. Med."},{"key":"2025021008001876700_r35","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1007\/s00125-016-4036-y","article-title":"LIGHT\/TNFSF14 is increased in patients with type 2 diabetes mellitus and promotes islet cell dysfunction and endothelial cell inflammation in vitro","volume":"59","author":"Halvorsen","year":"2016","journal-title":"Diabetologia"},{"key":"2025021008001876700_r36","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1158\/0008-5472.CAN-16-1655","article-title":"LIGHT elevation enhances immune eradication of colon cancer metastases","volume":"77","author":"Qiao","year":"2017","journal-title":"Cancer Res."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/210\/5\/590\/61470026\/ji2200652.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/210\/5\/590\/61470026\/ji2200652.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T08:02:22Z","timestamp":1739174542000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/210\/5\/590\/7932625"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,23]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2200652","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,3]]},"published":{"date-parts":[[2023,1,23]]}}}