{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T03:19:58Z","timestamp":1783739998250,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Immunomodulation with autoantigens potentially constitutes a specific and safe treatment for type 1 diabetes (T1D). Studies with GAD\u2010alum administrated subcutaneously have shown to be safe, but its efficacy has been inconclusive. Administration of GAD\u2010alum into the lymph nodes, aimed to optimise antigen presentation, has shown promising results in an open\u2010label clinical trial. Herein, we compared the immune response of the individuals included in the trial with a group who received GAD\u2010alum subcutaneously in a previous study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      Samples from T1D individuals collected 15\u00a0months after administration of either three doses 1\u00a0month apart of 4\u00a0\u03bcg GAD\u2010alum into lymph nodes (LN,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a012) or two doses 1\u00a0month apart of 20\u00a0\u03bcg subcutaneously (SC,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a012) were studied. GADA, GADA subclasses, GAD\n                      <jats:sub>65<\/jats:sub>\n                      \u2010induced cytokines, peripheral blood mononuclear cell proliferation, and T cells markers were analysed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Low doses of GAD\u2010alum into the lymph nodes induced higher GADA levels than higher doses administrated subcutaneously. Immune response in the LN group was characterised by changes in GADA subclasses, with a relative reduction of IgG1 and enhanced IgG2, IgG3, and IgG4 proportion, higher GAD\n                      <jats:sub>65<\/jats:sub>\n                      \u2010induced secretion of IL\u20105, IL\u201010, and TNF\u2010\u03b1, and reduction of cell proliferation and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. These changes were not observed after subcutaneous (SC) injections of GAD\u2010alum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GAD\u2010specific immune responses 15\u00a0months after lymph node injections of GAD\u2010alum differed from the ones induced by SC administration of the same autoantigen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dmrr.3500","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T18:48:56Z","timestamp":1633632536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Immune response differs between intralymphatic or subcutaneous administration of GAD\u2010alum in individuals with recent onset type 1 diabetes"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6458-2359","authenticated-orcid":false,"given":"Fabr\u00edcia","family":"Dietrich","sequence":"first","affiliation":[{"name":"Division of Pediatrics Department of Biomedical and Clinical Sciences Faculty of Medicine and Health Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Barcenilla","sequence":"additional","affiliation":[{"name":"Division of Pediatrics Department of Biomedical and Clinical Sciences Faculty of Medicine and Health Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Tavira","sequence":"additional","affiliation":[{"name":"Division of Pediatrics Department of Biomedical and Clinical Sciences Faculty of Medicine and Health Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanette","family":"Wahlberg","sequence":"additional","affiliation":[{"name":"Department of Endocrinology in Link\u00f6ping Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Department of Health, Medicine and Caring Sciences Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Faculty of Medical Sciences \u00d6rebro University  \u00d6rebro Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Achenbach","sequence":"additional","affiliation":[{"name":"Institute of Diabetes Research Helmholtz Zentrum M\u00fcnchen  Munich Germany"},{"name":"Forschergruppe Diabetes School of Medicine Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1695-5234","authenticated-orcid":false,"given":"Johnny","family":"Ludvigsson","sequence":"additional","affiliation":[{"name":"Division of Pediatrics Department of Biomedical and Clinical Sciences Faculty of Medicine and Health Sciences Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Crown Princess Victoria Children\u2019s Hospital  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaura","family":"Casas","sequence":"additional","affiliation":[{"name":"Division of Pediatrics Department of Biomedical and Clinical Sciences Faculty of Medicine and Health Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v10.i12.560"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(18)30112\u20108"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(18)30109\u20108"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.11.017"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2015.8"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804328"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(11)60895\u20107"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107096"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3440"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010016\u20104122\u20101"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010020\u201005227\u2010z"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1616343"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9391845"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.564921"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc07\u20102451"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.2144\/fsoa\u20102020\u20100078"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.06.001"},{"issue":"1","key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"525","DOI":"10.4049\/jimmunol.163.1.525","article-title":"Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen\u2010specific regulation","volume":"163","author":"Bonifacio E","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12\u20102251"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010002\u20100816\u20107"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.11.011"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1359\u20106101(97)00034\u20108"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.10.2348"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.10.031"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.06.033"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104702"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051630798"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425599"}],"container-title":["Diabetes\/Metabolism Research and Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dmrr.3500","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/dmrr.3500","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dmrr.3500","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T13:59:41Z","timestamp":1776434381000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dmrr.3500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,12]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1002\/dmrr.3500"],"URL":"https:\/\/doi.org\/10.1002\/dmrr.3500","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1002\/DMRR.3500\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1002\/DMRR.3500\/v1\/decision1","asserted-by":"object"}]},"ISSN":["1520-7552","1520-7560"],"issn-type":[{"value":"1520-7552","type":"print"},{"value":"1520-7560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,12]]},"assertion":[{"value":"2021-03-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e3500"}}