Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes
GAD-alum given into lymph nodes to type 1 diabetes patients participating in an open-label pilot trial resulted in preservation of C-peptide similar to promising results from other trials. Here, we compared the immunomodulatory effect of giving GAD-alum directly into lymph nodes versus that induced...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2018/9391845 |
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| author | Beatriz Tavira Hugo Barcenilla Jeannette Wahlberg Peter Achenbach Johnny Ludvigsson Rosaura Casas |
| author_facet | Beatriz Tavira Hugo Barcenilla Jeannette Wahlberg Peter Achenbach Johnny Ludvigsson Rosaura Casas |
| author_sort | Beatriz Tavira |
| collection | DOAJ |
| description | GAD-alum given into lymph nodes to type 1 diabetes patients participating in an open-label pilot trial resulted in preservation of C-peptide similar to promising results from other trials. Here, we compared the immunomodulatory effect of giving GAD-alum directly into lymph nodes versus that induced by subcutaneous administration. Samples from T1D patients (n=6) who received 4 μg GAD-alum into lymph nodes (LNs), followed by two booster injections one month apart, and from patients (n=6) who received two subcutaneous injections (SC) (20 μg) given one month apart were compared. GADA, IA-2A, GADA subclasses, IgE, GAD65-induced cytokines, PBMC proliferation, and T cell markers were analyzed. Lower doses of GAD-alum into LN induced higher GADA levels than SC injections and reduced proliferation and IgG1 GADA subclass, while enhancing IgG2, IgG3, and IgG4. The cytokine profile was dominated by the Th2-associated cytokine IL-13, and GAD65 stimulation induced activated CD4 T cells. Patients responding clinically best account for most of the immunological changes. In contrast, SC treatment resulted in predominant IgG1, predominant IFN-γ, higher proliferation, and activated CD4 and CD8 cells. Patients from the LN group with best metabolic outcome seemed to have common immune correlates related to the treatment. This trial is registered with DIAGNODE (NCT02352974, clinicaltrials.gov) and DIABGAD (NCT01785108, clinicaltrials.gov). |
| format | Article |
| id | doaj-art-a9bf6a588ced4339b006fb0bae63bd2c |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-a9bf6a588ced4339b006fb0bae63bd2c2025-02-03T01:12:35ZengWileyJournal of Diabetes Research2314-67452314-67532018-01-01201810.1155/2018/93918459391845Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 DiabetesBeatriz Tavira0Hugo Barcenilla1Jeannette Wahlberg2Peter Achenbach3Johnny Ludvigsson4Rosaura Casas5Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, SwedenDivision of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, SwedenDepartment of Endocrinology and Department of Medical and Health Sciences and Department of Clinical and Experimental Medicine, Linköping University, Linköping, SwedenInstitute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum Rechts der Isar, Technische Universität München, München, GermanyDivision of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, SwedenDivision of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Medicine and Health Sciences, Linköping University, Linköping, SwedenGAD-alum given into lymph nodes to type 1 diabetes patients participating in an open-label pilot trial resulted in preservation of C-peptide similar to promising results from other trials. Here, we compared the immunomodulatory effect of giving GAD-alum directly into lymph nodes versus that induced by subcutaneous administration. Samples from T1D patients (n=6) who received 4 μg GAD-alum into lymph nodes (LNs), followed by two booster injections one month apart, and from patients (n=6) who received two subcutaneous injections (SC) (20 μg) given one month apart were compared. GADA, IA-2A, GADA subclasses, IgE, GAD65-induced cytokines, PBMC proliferation, and T cell markers were analyzed. Lower doses of GAD-alum into LN induced higher GADA levels than SC injections and reduced proliferation and IgG1 GADA subclass, while enhancing IgG2, IgG3, and IgG4. The cytokine profile was dominated by the Th2-associated cytokine IL-13, and GAD65 stimulation induced activated CD4 T cells. Patients responding clinically best account for most of the immunological changes. In contrast, SC treatment resulted in predominant IgG1, predominant IFN-γ, higher proliferation, and activated CD4 and CD8 cells. Patients from the LN group with best metabolic outcome seemed to have common immune correlates related to the treatment. This trial is registered with DIAGNODE (NCT02352974, clinicaltrials.gov) and DIABGAD (NCT01785108, clinicaltrials.gov).http://dx.doi.org/10.1155/2018/9391845 |
| spellingShingle | Beatriz Tavira Hugo Barcenilla Jeannette Wahlberg Peter Achenbach Johnny Ludvigsson Rosaura Casas Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes Journal of Diabetes Research |
| title | Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes |
| title_full | Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes |
| title_fullStr | Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes |
| title_full_unstemmed | Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes |
| title_short | Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes |
| title_sort | intralymphatic glutamic acid decarboxylase alum administration induced th2 like specific immunomodulation in responder patients a pilot clinical trial in type 1 diabetes |
| url | http://dx.doi.org/10.1155/2018/9391845 |
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