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Immune response differs between intralymphatic or subcutaneous administration of GAD-alum in individuals with recent onset Type 1 diabetes
Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Örebro University, School of Medical Sciences. Department of Endocrinology in Linköping, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.ORCID iD: 0000-0003-4061-6830
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2022 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 38, no 3, article id e3500Article in journal (Refereed) Published
Abstract [en]

Aims: Immunomodulation with autoantigens potentially constitutes a specific and safe treatment for Type 1 diabetes (T1D). Studies with GAD-alum administrated subcutaneously have shown to be safe, but its efficacy has been inconclusive. Administration of GAD-alum into the lymph nodes, aimed to optimize antigen presentation, has shown promising results in an open-label clinical trial. Here we compared the immune response of the individuals included in the trial with a group who received GAD-alum subcutaneously in a previous study.

Materials and methods: Samples from T1D individuals collected 15 months after administration of either three doses 1 month apart of 4 μg GAD-alum into lymph nodes (LN, n=12) or two doses one month apart of 20 μg subcutaneously (SC, n=12) were studied. GADA, GADA subclasses, GAD65 -induced cytokines, PBMCs proliferation and T cells markers were analyzed.

Results: Low doses of GAD-alum into the lymph nodes induced higher GADA levels than higher doses administrated subcutaneously. Immune response in the LN group was characterized by changes in GADA subclasses, with a relative reduction of IgG1 and enhanced IgG2, IgG3 and IgG4 proportion, higher GAD65 -induced secretion of IL-5, IL-10 and TNF-α and reduction of cell proliferation and CD8+ T cells. These changes were not observed after subcutaneous injections of GAD-alum.

Conclusions: GAD-specific immune responses 15 months after lymph node injections of GAD-alum differed from the ones induced by subcutaneous administration of the same autoantigen.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022. Vol. 38, no 3, article id e3500
Keywords [en]
Autoantigen, FOXP3, Forkhead fox P3, GAD-alum, GAD65, GADA, Glutamic acid decarboxylase, Glutamic acid decarboxylase autoantibodies, Glutamic acid decarboxylase formulated in aluminum hydroxide, Intralymphatic, LN, Lymph node, Lymph nodes, MMTT, Mixed Meal Tolerance Test, PBMCs, Peripheral blood mononuclear cells, Subcutaneous, T1D, Type 1 diabetes, sSC
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-94834DOI: 10.1002/dmrr.3500ISI: 000715167400001PubMedID: 34611978Scopus ID: 2-s2.0-85116860606OAI: oai:DiVA.org:oru-94834DiVA, id: diva2:1601167
Funder
DiabetesfondenSwedish Child Diabetes Foundation
Note

Funding agency:

Diamyd Medical

Available from: 2021-10-07 Created: 2021-10-07 Last updated: 2024-01-02Bibliographically approved

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Wahlberg, Jeanette

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