Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell Autoantibodies
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–Immune Tolerance 2 (DiAPREV-IT 2) clin...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/3532685 |
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| _version_ | 1832565509667684352 |
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| author | Falastin Salami Lampros Spiliopoulos Marlena Maziarz Markus Lundgren Charlotte Brundin Rasmus Bennet Magnus Hillman Carina Törn Helena Elding Larsson |
| author_facet | Falastin Salami Lampros Spiliopoulos Marlena Maziarz Markus Lundgren Charlotte Brundin Rasmus Bennet Magnus Hillman Carina Törn Helena Elding Larsson |
| author_sort | Falastin Salami |
| collection | DOAJ |
| description | 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–Immune 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) (p=0.006), T-cells (103 cells/μL) (p=0.008), T-helper cells (103 cells/μL) (p=0.014), and cytotoxic T-cells (103 cells/μL) (p=0.023) compared to the placebo-treated children 18 months from first GAD-alum injection. This difference remained 24 months after the first treatment for lymphocytes (p=0.027), T-cells (p=0.022), T-helper cells (p=0.048), and cytotoxic T-cells (p=0.018). 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. |
| format | Article |
| id | doaj-art-5ce53b6a5f094f66804ff4401cd71d69 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-5ce53b6a5f094f66804ff4401cd71d692025-02-03T01:07:31ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/3532685Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell AutoantibodiesFalastin Salami0Lampros Spiliopoulos1Marlena Maziarz2Markus Lundgren3Charlotte Brundin4Rasmus Bennet5Magnus Hillman6Carina Törn7Helena Elding Larsson8Department of Clinical SciencesDepartment of Clinical SciencesDepartment of Clinical SciencesDepartment of Clinical SciencesDepartment of Clinical SciencesDepartment of Clinical SciencesDiabetes Research LaboratoryDepartment of Clinical SciencesDepartment of Clinical SciencesObjective. 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–Immune 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) (p=0.006), T-cells (103 cells/μL) (p=0.008), T-helper cells (103 cells/μL) (p=0.014), and cytotoxic T-cells (103 cells/μL) (p=0.023) compared to the placebo-treated children 18 months from first GAD-alum injection. This difference remained 24 months after the first treatment for lymphocytes (p=0.027), T-cells (p=0.022), T-helper cells (p=0.048), and cytotoxic T-cells (p=0.018). 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.http://dx.doi.org/10.1155/2022/3532685 |
| spellingShingle | Falastin Salami Lampros Spiliopoulos Marlena Maziarz Markus Lundgren Charlotte Brundin Rasmus Bennet Magnus Hillman Carina Törn Helena Elding Larsson Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell Autoantibodies Journal of Immunology Research |
| title | Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell Autoantibodies |
| title_full | Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell Autoantibodies |
| title_fullStr | Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell Autoantibodies |
| title_full_unstemmed | Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell Autoantibodies |
| title_short | Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell Autoantibodies |
| title_sort | long term gad alum treatment effect on different t cell subpopulations in healthy children positive for multiple beta cell autoantibodies |
| url | http://dx.doi.org/10.1155/2022/3532685 |
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