{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:39:15Z","timestamp":1793036355224,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1051228"],"award-info":[{"award-number":["1051228"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1099676"],"award-info":[{"award-number":["1099676"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT2042979"],"award-info":[{"award-number":["GNT2042979"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001782","name":"University of Melbourne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001782","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The development of food sensitisation (FS) and food allergy (FA) reflects complex interactions between genetic, environmental and immunological factors, which conventional univariate approaches may fail to capture. This exploratory study applied penalised regression to determine whether early\u2010life immune responses to common pathogens are associated with infant FS and FA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      At 1\u2009year of age, FS was determined by skin prick test and FA by allergy\/tolerance history and oral food challenge. Elastic net regression (ENR) was applied to cytokine response data (13 cytokines) from whole blood stimulation (11 microbial stimuli) collected at 6\u2009months of age (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009147), together with longitudinal clinical data from MIS BAIR trial infants. Stably selected variables (0.75) were analysed by multivariable logistic regression to explore the direction of association of the stably selected variables.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For FS, 13 cytokine\u2010stimulant pairs were stably selected in cytokine\u2010only ENR models. After including early\u2010life clinical factors, four pairs were retained. Two were inversely associated with FS (\n                      <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      IL\u20101Ra and Pam3CSK4 MIP\u20101\u03b1). Two were positively associated (\n                      <jats:italic>Streptococcus pyogenes<\/jats:italic>\n                      IL\u20101Ra and peptidoglycan IFN\u2010\u03b3). For FA, four cytokine\u2010stimulant pairs were selected in cytokine\u2010only ENR models. Two were positively associated with FA (\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      \u2010stimulated MCP\u20101 and\n                      <jats:italic>S. pyogenes<\/jats:italic>\n                      IP\u201010), and two inversely associated (Pam3CSK4 IL\u20101Ra and\n                      <jats:italic>H. influenzae<\/jats:italic>\n                      IL\u20101Ra). No cytokine responses were selected after inclusion of clinical factors in the FA model. The most consistently selected clinical factors were infant eczema for FS and topical corticosteroid treatment by 6\u2009months for FA likely due to disease severity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Early\u2010life cytokine responses to pathogens associated with FS and FA at 1\u2009year were identified through stability selection. While hypothesis\u2010generating, findings were consistent with a role for early immune perturbation in the development of food sensitisation.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/pai70513-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.70513","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:46:21Z","timestamp":1792665981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of early life anti\u2010pathogen immune responses with infant food sensitisation and allergy: An elastic\u2010net stability\u2010selection approach"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2295-4641","authenticated-orcid":false,"given":"Ellie","family":"McDonald","sequence":"first","affiliation":[{"name":"Infectious Diseases Group Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofie","family":"Biering\u2010S\u00f8rensen","sequence":"additional","affiliation":[{"name":"Infectious Diseases Group Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2395-4574","authenticated-orcid":false,"given":"Laure F.","family":"Pittet","sequence":"additional","affiliation":[{"name":"Infectious Diseases Group Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Paediatrics The University of Melbourne  Parkville Victoria Australia"},{"name":"Immunology, Vaccinology, Rheumatology and Infectious Diseases Unit Geneva University Hospitals and Faculty of Medicine  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3446-4594","authenticated-orcid":false,"given":"Nigel","family":"Curtis","sequence":"additional","affiliation":[{"name":"Infectious Diseases Group Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Paediatrics The University of Melbourne  Parkville Victoria Australia"},{"name":"Department of Infectious Diseases The Royal Children's Hospital Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8404-4462","authenticated-orcid":false,"given":"Nicole L.","family":"Messina","sequence":"additional","affiliation":[{"name":"Infectious Diseases Group Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Paediatrics The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.11.008"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph15092043"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.11.027"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15939"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00130832-200310000-00003"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.10.024"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad4322"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01344-4"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-032844"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.14537"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15022"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy069"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa030"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4614-6849-3"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v045.i03"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/asaa052"},{"key":"e_1_2_11_19_1","volume-title":"An R Companion to Applied Regression","author":"Fox J","year":"2019"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1201\/9780429492259"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jrsssc\/qlad058"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9868.2010.00740.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/80.1.27"},{"key":"e_1_2_11_24_1","volume-title":"The Elements of Statistical Learning. Data Mining, Inference, and Prediction","author":"Hastie T","year":"2017"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1994.tb08532.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1994.tb08530.x"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.140.12.1513"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2022.04.025"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.567981"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(99)70185-5"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.11.020"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.11.4.7917315"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(93)90250-7"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2026.07.011"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2021.13.3.404"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13389"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2020.12.2.322"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16095"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-34113-y"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxac013"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/mcn.13673"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002244"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2008.04.042"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013153"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/606383"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/pai.13246"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00140"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2007.04.003"},{"issue":"4","key":"e_1_2_11_49_1","first-page":"644","article-title":"Toll\u2010like receptors 2 and 4\u2010mediated reciprocal Th17 and antibody responses to group a streptococcus infection","volume":"215","author":"Wang X","year":"2017","journal-title":"J Infect Dis"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.18919"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.10.049"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13367"}],"container-title":["Pediatric Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pai.70513","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pai.70513","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pai.70513","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:01:56Z","timestamp":1793034116000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pai.70513"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":51,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/pai.70513"],"URL":"https:\/\/doi.org\/10.1111\/pai.70513","archive":["Portico"],"relation":{},"ISSN":["0905-6157","1399-3038"],"issn-type":[{"value":"0905-6157","type":"print"},{"value":"1399-3038","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-05-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70513"}}