{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T19:43:12Z","timestamp":1774554192101,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Department for International Development","award":["MR\/R007942\/1"],"award-info":[{"award-number":["MR\/R007942\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>As individuals progress through adolescence, their risk of tuberculosis (TB) increases, and the type of disease that develops changes, with increasing cavitary formation and parenchymal tissue destruction. While it is widely assumed that the changes in risk and disease phenotype are due to puberty exerting an impact on host immune responses to Mycobacterium tuberculosis, this relationship has been poorly studied.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Teen TB was an observational study that recruited 50 adolescents with pulmonary TB and 50 controls exposed to TB in Cape Town, South Africa. Blood was collected at baseline and again at month 2 from those with TB. Concentrations of 43 cytokines and 19 hormones were measured and compared between individuals with TB and controls, and changes were monitored over time in those with TB. The relationship between Tanner stage and cytokine\/endocrine concentrations was also assessed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>IL-1ra, IP-10, SAP, cortisol, lipocalin 2, and resistin were higher, while ghrelin, T3, and DHEAS were lower, in adolescents with TB vs healthy controls. DHEAS, progesterone, luteinizing hormone, testosterone, C peptide, estradiol, and cortisol were positively correlated and T3 negatively correlated with Tanner stage in healthy controls. In adolescents with TB, there was no association between Tanner stage and cytokine\/endocrine markers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>While in healthy individuals there was a strong association between Tanner stage and endocrine markers, this relationship was absent in adolescents with TB. TB disease appears to disrupt the normal physiologic process of puberty. This could have a substantial impact on growth and development for adolescents developing TB during this critical time.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf293","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T18:08:29Z","timestamp":1748887709000},"source":"Crossref","is-referenced-by-count":1,"title":["Impact of Puberty on Immune Responses to <i>Mycobacterium tuberculosis<\/i> in South African Adolescents"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1635-253X","authenticated-orcid":false,"given":"L\u00e9anie","family":"Kleynhans","sequence":"first","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]},{"name":"Mater Research Institute\u2013The University of Queensland, Translational Research Institute , Brisbane ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3402-169X","authenticated-orcid":false,"given":"Elizna","family":"Maasdorp","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for TB Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]},{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]},{"name":"School for Data Science and Computational Thinking, Stellenbosch University , Cape Town ,","place":["South Africa"]},{"name":"Centre for Bioinformatics and Computational Biology, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candice I","family":"Snyders","sequence":"additional","affiliation":[{"name":"DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, Division of Immunology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2296-2302","authenticated-orcid":false,"given":"James A","family":"Seddon","sequence":"additional","affiliation":[{"name":"Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University , Cape Town ,","place":["South Africa"]},{"name":"Department of Infectious Disease, Imperial College London ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"2025062705331867200_jiaf293-B1","author":"World Health Organisation"},{"key":"2025062705331867200_jiaf293-B2","doi-asserted-by":"crossref","first-page":"1702352","DOI":"10.1183\/13993003.02352-2017","article-title":"The incidence of tuberculosis among adolescents and young adults: a global estimate","volume":"51","author":"Snow","year":"2018","journal-title":"Eur Respir J"},{"key":"2025062705331867200_jiaf293-B3","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.3389\/fimmu.2018.02946","article-title":"The wonder years: what can primary school children teach us about immunity to Mycobacterium tuberculosis?","volume":"9","author":"Seddon","year":"2018","journal-title":"Front Immunol"},{"key":"2025062705331867200_jiaf293-B4","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S2352-4642(19)30337-2","article-title":"Adolescent tuberculosis","volume":"4","author":"Snow","year":"2020","journal-title":"Lancet Child Adolesc Health"},{"key":"2025062705331867200_jiaf293-B5","doi-asserted-by":"crossref","first-page":"e74","DOI":"10.1371\/journal.pmed.0050074","article-title":"Social contacts and mixing patterns relevant to the spread of infectious diseases","volume":"5","author":"Mossong","year":"2008","journal-title":"PLoS Med"},{"key":"2025062705331867200_jiaf293-B6","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1093\/aje\/kwr251","article-title":"Social mixing patterns within a South African township community: implications for respiratory disease transmission and control","volume":"174","author":"Johnstone-Robertson","year":"2011","journal-title":"Am J Epidemiol"},{"key":"2025062705331867200_jiaf293-B7","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s12916-019-1452-0","article-title":"Profiling Mycobacterium tuberculosis transmission and the resulting disease burden in the five highest tuberculosis burden countries","volume":"17","author":"Ragonnet","year":"2019","journal-title":"BMC Med"},{"key":"2025062705331867200_jiaf293-B8","first-page":"406","article-title":"Changing prevalence of tuberculosis infection with increasing age in high-burden townships in South Africa","volume":"14","author":"Wood","year":"2010","journal-title":"Int J Tuberc Lung Dis"},{"key":"2025062705331867200_jiaf293-B9","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1016\/S1473-3099(18)30157-9","article-title":"Tuberculosis susceptibility and protection in children","volume":"19","author":"Basu Roy","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2025062705331867200_jiaf293-B10","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/oxfordjournals.aje.a121593","article-title":"The prognosis of a positive tuberculin reaction in childhood and adolescence","volume":"99","author":"Comstock","year":"1974","journal-title":"Am J Epidemiol"},{"key":"2025062705331867200_jiaf293-B11","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1016\/S0140-6736(10)60580-6","article-title":"Age and the epidemiology and pathogenesis of tuberculosis","volume":"375","author":"Donald","year":"2010","journal-title":"Lancet"},{"key":"2025062705331867200_jiaf293-B12","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1210\/jcem-47-3-572","article-title":"Pattern of plasma dehydroepiandrosterone sulfate levels in humans from birth to adulthood: evidence for testicular production","volume":"47","author":"Peretti","year":"1978","journal-title":"J Clin Endocrinol Metab"},{"key":"2025062705331867200_jiaf293-B13","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1365-3083.2007.01952.x","article-title":"Altered cortisol\/DHEA ratio in tuberculosis patients and its relationship with abnormalities in the mycobacterial-driven cytokine production by peripheral blood mononuclear cells","volume":"66","author":"Bozza","year":"2007","journal-title":"Scand J Immunol"},{"key":"2025062705331867200_jiaf293-B14","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.yfrne.2016.12.003","article-title":"Puberty and structural brain development in humans","volume":"44","author":"Herting","year":"2017","journal-title":"Front Neuroendocrinol"},{"key":"2025062705331867200_jiaf293-B15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0165-5728(02)00357-0","article-title":"Cytokines and neuro-immune-endocrine interactions: a role for the hypothalamic-pituitary-adrenal revolving axis","volume":"133","author":"Haddad","year":"2002","journal-title":"J Neuroimmunol"},{"key":"2025062705331867200_jiaf293-B16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/sji.12413","article-title":"Effects of ageing on the immune system: infants to elderly","volume":"83","author":"Valiathan","year":"2016","journal-title":"Scand J Immunol"},{"key":"2025062705331867200_jiaf293-B17","first-page":"20143085","article-title":"Evolution of the immune system in humans from infancy to old age","volume":"282","author":"Simon","year":"2015","journal-title":"Proc Biol Sci"},{"key":"2025062705331867200_jiaf293-B18","doi-asserted-by":"crossref","first-page":"e1005374","DOI":"10.1371\/journal.ppat.1005374","article-title":"SeXX matters in infectious disease pathogenesis","volume":"12","author":"vom Steeg","year":"2016","journal-title":"PLoS Pathog"},{"key":"2025062705331867200_jiaf293-B19","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nri2394","article-title":"The X-files in immunity: sex-based differences predispose immune responses","volume":"8","author":"Fish","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"2025062705331867200_jiaf293-B20","doi-asserted-by":"crossref","first-page":"170077","DOI":"10.1183\/16000617.0077-2017","article-title":"Tuberculosis and lung damage: from epidemiology to pathophysiology","volume":"27","author":"Ravimohan","year":"2018","journal-title":"Eur Respir Rev"},{"key":"2025062705331867200_jiaf293-B21","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/0960-0760(91)90284-C","article-title":"Cytokines as modulators of the hypothalamus pituitary-adrenal axis","volume":"40","author":"Besedovsky","year":"1991","journal-title":"J Steroid Biochem"},{"key":"2025062705331867200_jiaf293-B22","first-page":"1455","article-title":"Sex hormone status and bone mineral density in men with rheumatoid arthritis","volume":"22","author":"Mateo","year":"1995","journal-title":"J Rheumatol"},{"key":"2025062705331867200_jiaf293-B23","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/BF03347683","article-title":"Hormonal pattern in women affected by rheumatoid arthritis","volume":"16","author":"Valentino","year":"1993","journal-title":"J Endocrinol Invest"},{"key":"2025062705331867200_jiaf293-B24","doi-asserted-by":"crossref","first-page":"e062979","DOI":"10.1136\/bmjopen-2022-062979","article-title":"Understanding the biology, morbidity and social contexts of adolescent tuberculosis: a prospective observational cohort study protocol (Teen TB)","volume":"12","author":"Swanepoel","year":"2022","journal-title":"BMJ Open"},{"key":"2025062705331867200_jiaf293-B25","volume-title":"Review of methods for determining pubertal status and age of onset of puberty in cohort and longitudinal studies","author":"Baird","year":"2017"},{"key":"2025062705331867200_jiaf293-B26","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2024"},{"key":"2025062705331867200_jiaf293-B27","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.bbi.2006.06.005","article-title":"Endocrine and cytokine responses in humans with pulmonary tuberculosis","volume":"21","author":"Rey","year":"2007","journal-title":"Brain Behav Immun"},{"key":"2025062705331867200_jiaf293-B28","doi-asserted-by":"crossref","first-page":"ftx087","DOI":"10.1093\/femspd\/ftx087","article-title":"The clinical recovery of tuberculosis patients undergoing specific treatment is associated with changes in the immune and neuroendocrine responses","volume":"75","author":"Diaz","year":"2017","journal-title":"Pathog Dis"},{"key":"2025062705331867200_jiaf293-B29","doi-asserted-by":"crossref","first-page":"639965","DOI":"10.3389\/fimmu.2021.639965","article-title":"Inflammatory determinants of differential tuberculosis risk in pre-adolescent children and young adults","volume":"12","author":"Baguma","year":"2021","journal-title":"Front Immunol"},{"key":"2025062705331867200_jiaf293-B30","doi-asserted-by":"crossref","first-page":"690","DOI":"10.3389\/fimmu.2017.00690","article-title":"Changes in host immune-endocrine relationships during tuberculosis treatment in patients with cured and failed treatment outcomes","volume":"8","author":"Kleynhans","year":"2017","journal-title":"Front Immunol"},{"key":"2025062705331867200_jiaf293-B31","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.tube.2011.04.007","article-title":"Treatment end point determinants for pulmonary tuberculosis: human resistin as a surrogate biomarker","volume":"91","author":"Ehtesham","year":"2011","journal-title":"Tuberculosis"},{"key":"2025062705331867200_jiaf293-B32","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1210\/jcem.87.2.8228","article-title":"Decreased plasma leptin concentrations in tuberculosis patients are associated with wasting and inflammation","volume":"87","author":"van Crevel","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2025062705331867200_jiaf293-B33","doi-asserted-by":"crossref","first-page":"e1006676","DOI":"10.1371\/journal.ppat.1006676","article-title":"Mycobacterium tuberculosis infection modulates adipose tissue biology","volume":"13","author":"Beigier-Bompadre","year":"2017","journal-title":"PLoS Pathog"},{"key":"2025062705331867200_jiaf293-B34","doi-asserted-by":"crossref","first-page":"L726","DOI":"10.1152\/ajplung.00080.2021","article-title":"Comprehensive review of lipocalin 2\u2013mediated effects in lung inflammation","volume":"321","author":"Guardado","year":"2021","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2025062705331867200_jiaf293-B35","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.3389\/fimmu.2018.02717","article-title":"Lipocalin-2 functions as inhibitor of innate resistance to Mycobacterium tuberculosis","volume":"9","author":"Dahl","year":"2018","journal-title":"Front Immunol"},{"key":"2025062705331867200_jiaf293-B36","doi-asserted-by":"crossref","first-page":"8521","DOI":"10.4049\/jimmunol.181.12.8521","article-title":"Lipocalin 2\u2013dependent inhibition of mycobacterial growth in alveolar epithelium","volume":"181","author":"Saiga","year":"2008","journal-title":"J Immunol"},{"key":"2025062705331867200_jiaf293-B37","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.micinf.2014.11.009","article-title":"Increased resistin may suppress reactive oxygen species production and inflammasome activation in type 2 diabetic patients with pulmonary tuberculosis infection","volume":"17","author":"Chao","year":"2015","journal-title":"Microbes Infect"},{"key":"2025062705331867200_jiaf293-B38","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.it.2022.06.004","article-title":"Genetic and hormonal mechanisms underlying sex-specific immune responses in tuberculosis","volume":"43","author":"Gupta","year":"2022","journal-title":"Trends Immunol"},{"key":"2025062705331867200_jiaf293-B39","doi-asserted-by":"crossref","first-page":"e1000199","DOI":"10.1371\/journal.pmed.1000199","article-title":"Sexual inequality in tuberculosis","volume":"6","author":"Neyrolles","year":"2009","journal-title":"PLoS Med"},{"key":"2025062705331867200_jiaf293-B40","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1196\/annals.1351.015","article-title":"Effects of testosterone, 17beta-estradiol, and downstream estrogens on cytokine secretion from human leukocytes in the presence and absence of cortisol","volume":"1069","author":"Janele","year":"2006","journal-title":"Ann N Y Acad Sci"},{"key":"2025062705331867200_jiaf293-B41","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/00126334-200305010-00009","article-title":"Delayed onset of pubertal development in children and adolescents with perinatally acquired HIV infection","volume":"33","author":"Buchacz","year":"2003","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2025062705331867200_jiaf293-B42","doi-asserted-by":"crossref","first-page":"S88","DOI":"10.1016\/j.jcf.2019.08.013","article-title":"Puberty in cystic fibrosis","volume":"18(Suppl 2)","author":"Goldsweig","year":"2019","journal-title":"J Cyst Fibros"},{"key":"2025062705331867200_jiaf293-B43","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.coemr.2020.06.002","article-title":"Puberty in type 1 diabetes mellitus: advances in care are associated with changes in pubertal milestones and hormone profiles","volume":"14","author":"Codner","year":"2020","journal-title":"Curr Opin Endocr Metab Res"},{"key":"2025062705331867200_jiaf293-B44","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1203\/00006450-200302000-00002","article-title":"Delayed puberty associated with inflammatory bowel disease","volume":"53","author":"Ballinger","year":"2003","journal-title":"Pediatr Res"},{"key":"2025062705331867200_jiaf293-B45","doi-asserted-by":"crossref","first-page":"e20163177","DOI":"10.1542\/peds.2016-3177","article-title":"Adult consequences of self-limited delayed puberty","volume":"139","author":"Zhu","year":"2017","journal-title":"Pediatrics"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaf293\/63419123\/jiaf293.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiaf293\/63419123\/jiaf293.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T09:33:30Z","timestamp":1751016810000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/advance-article\/doi\/10.1093\/infdis\/jiaf293\/8155333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":45,"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiaf293","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]},"article-number":"jiaf293"}}