{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:57:07Z","timestamp":1771232227018,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish Childhood Diabetes Foundation"},{"name":"Sk\u00e5ne County Council for Research and Development"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2022,5,25]]},"abstract":"<jats:p>Objective. The objective of this study was to explore whether recombinant GAD65 conjugated hydroxide (GAD-alum) treatment affected peripheral blood T-cell subpopulations in healthy children with multiple beta cell autoantibodies. Method. The Diabetes Prevention\u2013Immune Tolerance 2 (DiAPREV-IT 2) clinical trial enrolled 26 children between 4 and 13 years of age, positive for glutamic acid decarboxylase autoantibody (GADA) and at least one other autoantibody (insulin, insulinoma antigen-2, or zinc transporter 8 autoantibody (IAA, IA-2A, or ZnT8A)) at baseline. The children were randomized to two doses of subcutaneously administered GAD-alum treatment or placebo, 30 days apart. Complete blood count (CBC) and immunophenotyping of T-cell subpopulations by flow cytometry were performed regularly during the 24 months of follow-up posttreatment. Cross-sectional analyses were performed comparing lymphocyte and T-cell subpopulations between GAD-alum and placebo-treated subjects. Results. GAD-alum-treated children had lower levels of lymphocytes (109 cells\/L) (<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>p<\/a:mi>\n                        <a:mo>=<\/a:mo>\n                        <a:mn>0.006<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>), T-cells (103 cells\/\u03bcL) (<jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>p<\/c:mi>\n                        <c:mo>=<\/c:mo>\n                        <c:mn>0.008<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>), T-helper cells (103 cells\/\u03bcL) (<jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mi>p<\/e:mi>\n                        <e:mo>=<\/e:mo>\n                        <e:mn>0.014<\/e:mn>\n                     <\/e:math>\n                  <\/jats:inline-formula>), and cytotoxic T-cells (103 cells\/\u03bcL) (<jats:inline-formula>\n                     <g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                        <g:mi>p<\/g:mi>\n                        <g:mo>=<\/g:mo>\n                        <g:mn>0.023<\/g:mn>\n                     <\/g:math>\n                  <\/jats:inline-formula>) compared to the placebo-treated children 18 months from first GAD-alum injection. This difference remained 24 months after the first treatment for lymphocytes (<jats:inline-formula>\n                     <i:math xmlns:i=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\">\n                        <i:mi>p<\/i:mi>\n                        <i:mo>=<\/i:mo>\n                        <i:mn>0.027<\/i:mn>\n                     <\/i:math>\n                  <\/jats:inline-formula>), T-cells (<jats:inline-formula>\n                     <k:math xmlns:k=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\">\n                        <k:mi>p<\/k:mi>\n                        <k:mo>=<\/k:mo>\n                        <k:mn>0.022<\/k:mn>\n                     <\/k:math>\n                  <\/jats:inline-formula>), T-helper cells (<jats:inline-formula>\n                     <m:math xmlns:m=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\">\n                        <m:mi>p<\/m:mi>\n                        <m:mo>=<\/m:mo>\n                        <m:mn>0.048<\/m:mn>\n                     <\/m:math>\n                  <\/jats:inline-formula>), and cytotoxic T-cells (<jats:inline-formula>\n                     <o:math xmlns:o=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\">\n                        <o:mi>p<\/o:mi>\n                        <o:mo>=<\/o:mo>\n                        <o:mn>0.018<\/o:mn>\n                     <\/o:math>\n                  <\/jats:inline-formula>). Conclusion. Our findings suggest that levels of total T-cells and T-cell subpopulations declined 18 and 24 months after GAD-alum treatment in healthy children with multiple beta-cell autoantibodies including GADA.<\/jats:p>","DOI":"10.1155\/2022\/3532685","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T02:20:05Z","timestamp":1653531605000},"page":"1-17","source":"Crossref","is-referenced-by-count":4,"title":["Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell Autoantibodies"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0098-4287","authenticated-orcid":true,"given":"Falastin","family":"Salami","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences, Lund University\/Clinical Research Centre, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lampros","family":"Spiliopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University\/Clinical Research Centre, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marlena","family":"Maziarz","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University\/Clinical Research Centre, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Lundgren","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University\/Clinical Research Centre, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"},{"name":"Department of Pediatrics, Kristianstad Hospital, Kristianstad, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Brundin","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University\/Clinical Research Centre, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rasmus","family":"Bennet","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University\/Clinical Research Centre, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magnus","family":"Hillman","sequence":"additional","affiliation":[{"name":"Diabetes Research Laboratory, Department of Clinical Sciences, Faculty of Medicine, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carina","family":"T\u00f6rn","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University\/Clinical Research Centre, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3306-1742","authenticated-orcid":true,"given":"Helena","family":"Elding Larsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Lund University\/Clinical Research Centre, Sk\u00e5ne University Hospital, Malm\u00f6, Sweden"},{"name":"Department of Pediatrics, Sk\u00e5ne University Hospital, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"issue":"21","key":"1","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1056\/NEJM198605223142106","article-title":"Type I diabetes mellitus. 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