{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T08:50:06Z","timestamp":1781081406283,"version":"3.54.1"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,10,11]],"date-time":"2007-10-11T00:00:00Z","timestamp":1192060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Pediatric\u2010onset multiple sclerosis offers a unique window into early targets and mechanisms of immune dysregulation. It is unknown whether heightened T\u2010cell reactivities documented in adult patients, to both target\u2010organ and environmental antigens, emerge in parallel or develop as early or late events. Our objectives were to determine the presence, pattern, and specificity of abnormal T\u2010cell reactivities to such antigens in the earliest stages of the multiple sclerosis process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral T\u2010cell proliferative responses to self\u2010, dietary, and control antigens were blindly evaluated in a large cohort of well\u2010characterized children (n = 172) with central nervous system (CNS) inflammatory demyelination (n = 63), recent\u2010onset type 1 (insulin\u2010dependent) diabetes mellitus (T1D; n = 41), nonautoimmune neurological conditions (n = 39), and healthy children (n = 29).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Children with inflammatory demyelination, CNS injury, and T1D exhibited heightened T\u2010cell reactivities to self\u2010antigens, and these responses were not strictly limited to the disease target organs. Children with autoimmune disease and CNS injury also exhibited abnormal T\u2010cell responses against multiple cow\u2010milk proteins. Responses to specific milk epitopes distinguished T1D from inflammatory demyelination and other neurological diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Abnormal T\u2010cell reactivities to self\u2010 and environmental antigens manifest in the earliest clinical stages of inflammatory demyelination and T1D. The pattern of heightened T\u2010cell reactivities implicates both shared and distinct mechanisms of immune dysregulation in the different autoimmune diseases. Abnormal T\u2010cell responses in children with tissue injury challenge the prevailing view that CNS autoreactive cells inherently mediate the disease in early multiple sclerosis. Ann Neurol 2007<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21244","type":"journal-article","created":{"date-parts":[[2007,10,11]],"date-time":"2007-10-11T21:17:32Z","timestamp":1192137452000},"page":"98-111","source":"Crossref","is-referenced-by-count":72,"title":["Abnormal T\u2010cell reactivities in childhood inflammatory demyelinating disease and type 1 diabetes"],"prefix":"10.1002","volume":"63","author":[{"given":"Brenda","family":"Banwell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Bar\u2010Or","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren B.","family":"Krupp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy J.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Michael","family":"Dosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,10,11]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2005.00240.x"},{"key":"e_1_2_7_3_2","first-page":"91","article-title":"Human immune studies in multiple sclerosis","volume":"98","author":"Bar\u2010Or A","year":"2006","journal-title":"Adv Neurol"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21117"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21141"},{"key":"e_1_2_7_6_2","first-page":"181","article-title":"Ultraviolet radiation and autoimmune disease: insights from epidemiological research","author":"Ponsonby AL","year":"2002","journal-title":"Toxicology"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-9877(86)90057-5"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000110946"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199207303270509"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199211263272217"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199312163292505"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-209-43897C"},{"key":"e_1_2_7_13_2","doi-asserted-by":"crossref","first-page":"557","DOI":"10.2337\/diab.46.4.557","article-title":"Immunological aspects of nutritional diabetes prevention in NOD mice: a pilot study for the cow's milk\u2010based IDDM prevention trial","volume":"46","author":"Karges W","year":"1997","journal-title":"Diabetes"},{"key":"e_1_2_7_14_2","first-page":"125","volume-title":"Principles of neuroepidemiology","author":"Bar\u2010Or A","year":"2001"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.5.2859"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-005-1733-3"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.7.4751"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250100611"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2004.01.002"},{"key":"e_1_2_7_20_2","doi-asserted-by":"crossref","first-page":"6933","DOI":"10.4049\/jimmunol.163.12.6933","article-title":"Persistent T cell anergy in human type 1 diabetes","volume":"163","author":"Dosch H","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1032"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410130302"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000259422.44235.a8"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.2337\/db05-1378"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.4.2831"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm818"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(94)90123-6"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.5.1375"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1191\/135248506ms1282oa"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1998.tb01210.x"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20316"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-006-9144-5"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.10.038"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0098-2997(95)00001-W"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1212160"},{"key":"e_1_2_7_36_2","first-page":"427","article-title":"The distribution of multiple sclerosis in relation to the dairy industry and milk consumption","volume":"83","author":"Butcher J","year":"1976","journal-title":"N Z Med J"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.15.1875"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1444"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.21244","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.21244","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T01:12:19Z","timestamp":1695949939000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.21244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,10,11]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,1]]}},"alternative-id":["10.1002\/ana.21244"],"URL":"https:\/\/doi.org\/10.1002\/ana.21244","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,10,11]]}}}