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Axelsson, Stina
Publications (10 of 19) Show all publications
Ludvigsson, J., Chéramy, M., Axelsson, S., Pihl, M., Åkerman, L. & Casas, R. (2014). GAD-treatment of children and adolescents with recent-onset Type 1 diabetes preserves residual insulin secretion after 30 months. Diabetes/Metabolism Research Reviews, 30(5), 405-414
Open this publication in new window or tab >>GAD-treatment of children and adolescents with recent-onset Type 1 diabetes preserves residual insulin secretion after 30 months
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2014 (English)In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 30, no 5, p. 405-414Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: This study aimed to analyse data from two different studies (Phase II and Phase III) regarding the safety and efficacy of treatment with alum formulated glutamic acid decarboxylase GAD65 (GAD-alum), 30 months after administration to children and adolescents with Type 1 diabetes (T1D).

METHODS: The Phase II trial was a double-blind, randomized placebo-controlled study, including 70 children and adolescents which were followed for 30 months. Participants received a subcutaneous injection of either 20 µg of GAD-alum or placebo at baseline and one month later. During a subsequent larger European Phase III trial including three treatment arms, participants received two or four subcutaneous injections of either 20 µg of GAD-alum and/or placebo at baseline, 1, 3 and 9 months. The Phase III trial was prematurely interrupted at 15 months, but of the 148 Swedish patients, a majority completed the 21 months follow-up and 45 patients completed the trial at 30 months. Both studies included GADA-positive patients with fasting C-peptide ≥0.10 nmol/l. We have now combined the results of these two trials.

RESULTS: There were no treatment related adverse events. In patients treated with 2 GAD-alum doses, stimulated C-peptide AUC had decreased significantly less (9 m: p < 0.037; 15 m p < 0.032; 21 m p < 0.003 and 30 m p < 0.004) and a larger proportion of these patients were also able to achieve a peak stimulated C-peptide >0.2 nmol/l (p < 0.05), as compared to placebo.

CONCLUSION: Treatment with two doses of GAD-alum in children and adolescents with recent-onset T1D shows no adverse events and preserves residual insulin secretion. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2014
Keywords
arrays; celiac disease; children; gene expression; gluten-free diet; IL-17; mucosa; Th17
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-108613 (URN)10.1002/dmrr.2503 (DOI)000339416900007 ()24302596 (PubMedID)
Available from: 2014-07-01 Created: 2014-07-01 Last updated: 2017-12-05Bibliographically approved
Axelsson, S., Cheramy, M., Åkerman, L., Pihl, M., Ludvigsson, J. & Casas, R. (2013). Cellular and Humoral Immune responses in Type 1 Diabetic patients participating in a Phase III GAD-alum Intervention Trial. Diabetes Care, 36(11), 3418-3424
Open this publication in new window or tab >>Cellular and Humoral Immune responses in Type 1 Diabetic patients participating in a Phase III GAD-alum Intervention Trial
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2013 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 11, p. 3418-3424Article in journal (Refereed) Published
Abstract [en]

OBJECTIVEGAD formulated in aluminum hydroxide (GAD-alum) has previously been shown to induce preservation of residual insulin secretion in recent-onset type 1 diabetes, but recent phase II and III GAD-alum trials failed to reach primary outcomes. The European phase III study was therefore closed after 15 months, and only a minority of patients completed the 30 months of follow-up.RESEARCH DESIGN AND METHODSThis study aimed to characterize cellular and humoral responses in the Swedish patients (n = 148) participating in the phase III trial, receiving four (4D) or two (2D) GAD-alum doses or placebo. Serum GAD(65) antibody (GADA) levels, GADA IgG1-4 subclass distribution, cytokine secretion, and proliferative responses in peripheral blood mononuclear cells (PBMCs) were analyzed.RESULTSThe GAD(65)-induced cytokine profile tended to switch toward a predominant Th2-associated profile over time both in the 2D and 4D group. The groups also displayed increased GADA levels and PBMC proliferation compared with placebo, whereas GADA IgG subclass distribution changed in 4D patients.CONCLUSIONSBoth 2D and 4D patients displayed GAD(65)-specifc cellular and humoral effects after GAD-alum treatment, but at different time points and magnitudes. No specific immune markers could be associated with treatment efficacy.

Place, publisher, year, edition, pages
American Diabetes Association, 2013
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-99798 (URN)10.2337/dc12-2251 (DOI)000326274100013 ()23863909 (PubMedID)
Available from: 2013-10-21 Created: 2013-10-21 Last updated: 2017-12-06Bibliographically approved
Pihl, M., Axelsson, S., Cheramy, M., Reijonen, H., Ludvgisson, J. & Casas, R. (2013). GAD-alum treatment induces GAD-specific CD4 T cells in a phase III clinical trial.
Open this publication in new window or tab >>GAD-alum treatment induces GAD-specific CD4 T cells in a phase III clinical trial
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2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Glutamic Acid Decarboxylase (GAD)65 formulated in aluminium hydroxide (GAD-alum preserved insulin secretion in a phase II clinical trial in recent onset type 1 diabetes. GADalum treated patients up-regulated FOXP3 upon antigen recall at 21 and 30 months after treatment. A 4-year follow-up of the study revealed increased frequencies of both CD25+CD127+ and CD25hiCD127lo cells in treated patients after antigen recall. A subsequent european phase III trial was closed after 15 months after failing to reach primary outcome. We monitored antigen recall induced frequencies of memory, effector and regulatory T cells throughout the phase III trial. Antigen recall induced mainly CD25+CD127+, CD45RO+ and non-suppressive FOXP3loCD45RA- cells in GAD-alum treated patients. In addition, a population of activated FSChiSSChi cells was observed, enriched in CD25+CD127+, CD45RO+ and proliferating cells. GAD65-specific T cells determined by tetramer staining were induced by antigen recall in GAD-alum treated patients and were more frequent in the FSChiSSChi population. Additional doses of GAD-alum increased frequencies of CD25+CD127+, CD45RO+ and FSChiSSChi cells but had no effect on frequencies of CD25hiCD127lo. Our findings indicate that antigen recall after GAD-alum treatment primarily induces memory and activated T cells. In particular, GAD65-specific cells were mainly of a memory or activated phenotype. Additional doses of GAD-alum mainly affect memory T cell frequency and T cell activation.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-98251 (URN)
Available from: 2013-10-04 Created: 2013-10-04 Last updated: 2013-10-04
Pihl, M., Åkerman, L., Axelsson, S., Chéramy, M., Hjorth, M., Mallone, R., . . . Casas, R. (2013). Regulatory T cell phenotype and function 4 years after GAD–alum treatment in children with type 1 diabetes. Clinical and Experimental Immunology, 172(3), 394-402
Open this publication in new window or tab >>Regulatory T cell phenotype and function 4 years after GAD–alum treatment in children with type 1 diabetes
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2013 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 172, no 3, p. 394-402Article in journal (Refereed) Published
Abstract [en]

Glutamic acid decarboxylase (GAD)65 formulated with aluminium hydroxide (GAD-alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent-onset type 1 diabetes. In addition, GAD-alum treated patients increased CD4+CD25hi forkhead box protein 3+ (FoxP3+) cell numbers in response to in-vitro GAD65 stimulation. We have carried out a 4-year follow-up study of 59 of the original 70 patients to investigate long-term effects on the frequency and function of regulatory T cells after GAD-alum treatment. Peripheral blood mononuclear cells were stimulated in vitro with GAD65 for 7 days and expression of regulatory T cell markers was measured by flow cytometry. Regulatory T cells (CD4+CD25hiCD127lo) and effector T cells (CD4+CD25CD127+) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD-alum treatment. GAD-alum-treated patients displayed higher frequencies of in-vitro GAD65-induced CD4+CD25+CD127+ as well as CD4+CD25hiCD127lo and CD4+FoxP3+ cells compared to placebo. Moreover, GAD65 stimulation induced a population of CD4hi cells consisting mainly of CD25+CD127+, which was specific of GAD-alum-treated patients (16 of 25 versus one of 25 in placebo). Assessment of suppressive function in expanded regulatory T cells revealed no difference between GAD-alum- and placebo-treated individuals. Regulatory T cell frequency did not correlate with C-peptide secretion throughout the study. In conclusion, GAD-alum treatment induced both GAD65-reactive CD25+CD127+ and CD25hiCD127lo cells, but no difference in regulatory T cell function 4 years after GAD-alum treatment.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
Keywords
CD4 T cells (T helper, Th0, Th1, Th2, Th3, Th17), diabetes, immune regulation, regulatory T cells (Treg), therapy/immunotherapy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-93379 (URN)10.1111/cei.12078 (DOI)000318073000004 ()
Note

Funding Agencies|Swedish Research Council|K2008-55x-20652-01-3|Swedish Child Diabetes Foundation (Barndiabetesfonden)||Medical Research Council of Southeast Sweden||JDRF|1-2008-106|Ile-de-France CODDIM||Inserm Avenir Program||

Available from: 2013-05-31 Created: 2013-05-31 Last updated: 2017-12-06Bibliographically approved
Axelsson, S., Hjorth, M., Ludvigsson, J. & Casas, R. (2012). Decreased GAD(65) -specific Th1/Tc1 phenotype in children with Type 1 diabetes treated with GAD-alum.. Diabetic Medicine, 29(10), 1272-1278
Open this publication in new window or tab >>Decreased GAD(65) -specific Th1/Tc1 phenotype in children with Type 1 diabetes treated with GAD-alum.
2012 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 10, p. 1272-1278Article in journal (Refereed) Published
Abstract [en]

Aim  The balance between T helper cell subsets is an important regulator of the immune system and is often examined after immune therapies. We aimed to study the immunomodulatory effect of glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) in children with Type 1 diabetes, focusing on chemokines and their receptors. Methods  Blood samples were collected from 70 children with Type 1 diabetes included in a phase II clinical trial with GAD-alum. Expression of CC chemokine receptor 5 (CCR5) and CCR4 was analysed on CD4+ and CD8+ lymphocytes after in vitro stimulation with GAD(65) using flow cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in peripheral blood mononuclear cell supernatants with Luminex. Results  Expression of Th1-associated CCR5 was down-regulated following antigen challenge, together with an increased CCR4/CCR5 ratio and CCL2 secretion in GAD-alum-treated patients, but not in the placebo group. Conclusion  Our results suggest that GAD-alum treatment has induced a favourable immune modulation associated with decreased Th1/Tc1 phenotypes upon antigen re-challenge, which may be of importance for regulating GAD(65) immunity. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2012
Keywords
Type 1 diabetes, GAD(65), immunomodulation, chemokines, chemokine receptors
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-77745 (URN)10.1111/j.1464-5491.2012.03710.x (DOI)000308960400014 ()22587593 (PubMedID)
Note

funding agencies|Swedish Research Council|K2008-55x-20652-01-3|Swedish Child Diabetes Foundation (Barndiabetesfonden) Diamyd Medical||Medical Research Council of Southeast Sweden||

Available from: 2012-05-28 Created: 2012-05-28 Last updated: 2017-12-07
Axelsson, S. (2012). GAD65 An Immunomodulator in Type 1 Diabetes. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>GAD65 An Immunomodulator in Type 1 Diabetes
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Type 1 diabetes (T1D) is caused by a deficiency of insulin as a result of an autoimmune destruction of the pancreatic ² -cells. A possibility to preserve remaining ² -cells in children with newly diagnosed T1D is of great importance since sustained ² -cell function is recognized to result in reduced end-organ complications. Glutamic acid decarboxylase 65 (GAD65) is one of the major antigens targeted by self-reactive T cells in T1D, and immunomodulation with GAD65 formulated in aluminum (GAD-alum) has been considered both in prevention and treatment of T1D. Results from a Phase II trial have shown clinical effect of subcutaneous injections with GAD-alum, this was unfortunately not fully confirmed in the following larger Phase III trial which therefore was closed after 15 months. The general aim of this thesis was to study the immunomodulatory effect of GAD-alum-treatment in children with T1D participating in the Phase II and Phase III trials. We hypothesized that treatment with GAD-alum contributes to the preservation of residual insulin secretion through deviation of the GAD65-specific immune response from a destructive to a protective process, accompanied by a shift from T helper (Th) 1 towards a predominant Th2 profile. In the Phase II trial, GAD-alum-treated patients responded with an early GAD65-specific Th2 skewed cytokine secretion, with highest IL-5 and IL-13 secretion in clinical responders. Also, the CCR4/CCR5 ratio indicating balance between Th2/Tc2 and Th1/Tc1 responses, increased in treated patients. The recall response to GAD65 was characterized by a wide range of cytokines, but the relative contribution of each cytokine suggests a shift towards a more pronounced Th2-associated profile over time. Induction of a CD4+ cell subset upon GAD65-stimulation 4 years after treatment, suggesting clonal expansion of the memory T-cell compartment upon antigen re-challenge, was seen in parallel to a persistent GAD65-specific cytokine response. Finally, even if the phase III trial failed to reach the primary endpoint at 15 months, a subgroup analysis showed that the treatment had an effect on preservation of residual insulin secretion, but the effect was not seen until after 30 months. Taken together, these results suggest that GAD-alum treatment might exert its effect through induction of an early Th2 skewed immune response which tends to deviate away from a destructive Th1/Tc1 response upon GAD65 re-challenge, and generation of GAD65-specific memory T cells that produce cytokines and exert effector responses which may be important for regulating GAD65 immunity. Continued research to better understand how immunomodulation with autoantigen modifies T-cell responses and also which patients are suitable for treatment, is crucial for optimizing future intervention trials using ² -cell antigens.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. p. 81
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1310
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-77747 (URN)978-91-7519-888-0 (ISBN)
Public defence
2012-06-01, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2012-05-28 Created: 2012-05-28 Last updated: 2012-05-28Bibliographically approved
Martinuzzi, E., Gagnerault, M. C., Fourlanos, S., Harrison, L., Axelsson, S., Chéramy, M., . . . Mallone, R. (2012). Why are the benefits of vaccinations in the helping of beta-cellular antigenes in type 1 diabetes so limited? An analysis of linked immunological biomarkers in DIABETES and METABOLISM, vol 38, issue 2, pp A5-A5. In: DIABETES and METABOLISM (pp. A5-A5). Elsevier Masson, 38(2)
Open this publication in new window or tab >>Why are the benefits of vaccinations in the helping of beta-cellular antigenes in type 1 diabetes so limited? An analysis of linked immunological biomarkers in DIABETES and METABOLISM, vol 38, issue 2, pp A5-A5
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2012 (English)In: DIABETES and METABOLISM, Elsevier Masson , 2012, Vol. 38, no 2, p. A5-A5Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Elsevier Masson, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-77337 (URN)000302819400022 ()
Available from: 2012-05-11 Created: 2012-05-11 Last updated: 2012-05-11
Ludvigsson, J., Hjorth, M., Chéramy, M., Axelsson, S., Pihl, M., Forsander, G., . . . Casas, R. (2011). Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial. DIABETOLOGIA, 54(3), 634-640
Open this publication in new window or tab >>Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial
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2011 (English)In: DIABETOLOGIA, ISSN 0012-186X, Vol. 54, no 3, p. 634-640Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD(65) (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 mu g of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with andlt; 6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GAD-alum group fasting C-peptide was 0.332 +/- 0.032 nmol/l at day 1 and 0.215 +/- 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354 +/- 0.039 and 0.184 +/- 0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GAD-alum group than in the placebo-treated group after 4 years. Four years after treatment with GAD-alum, children and adolescents with recent-onset type 1 diabetes continue to show no adverse events and possibly to show clinically relevant preservation of C-peptide. ClinicalTrials.gov NCT00435981 The study was funded by The Swedish Research Council K2008-55X-20652-01-3, Barndiabetesfonden (The Swedish Child Diabetes Foundation), the Research Council of Southeast Sweden, and an unrestricted grant from Diamyd Medical AB.

Place, publisher, year, edition, pages
Springer Science Business Media, 2011
Keywords
C-peptide, Children, GAD-alum treatment, Immune modulation, Type 1 diabetes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-66310 (URN)10.1007/s00125-010-1988-1 (DOI)000286987000021 ()
Note
The original publication is available at www.springerlink.com: Johnny Ludvigsson, Maria Hjorth, Mikael Chéramy, Stina Axelsson, Mikael Pihl, G Forsander, N -O Nilsson, B-O Samuelsson, T Wood, J Aman, E Ortqvist and Rosaura Casas, Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial, 2011, DIABETOLOGIA, (54), 3, 634-640. http://dx.doi.org/10.1007/s00125-010-1988-1 Copyright: Springer Science Business Media http://www.springerlink.com/ Available from: 2011-03-11 Created: 2011-03-11 Last updated: 2011-03-24
Hjorth, M., Axelsson, S., Ryden, A., Faresjo, M., Ludvigsson, J. & Casas, R. (2011). GAD-alum treatment induces GAD(65)-specific CD4(+)CD25(high)FOXP3(+) cells in type 1 diabetic patients. CLINICAL IMMUNOLOGY, 138(1), 117-126
Open this publication in new window or tab >>GAD-alum treatment induces GAD(65)-specific CD4(+)CD25(high)FOXP3(+) cells in type 1 diabetic patients
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2011 (English)In: CLINICAL IMMUNOLOGY, ISSN 1521-6616, Vol. 138, no 1, p. 117-126Article in journal (Refereed) Published
Abstract [en]

Type 1 diabetes results from autoimmune destruction of insulin producing pancreatic beta-cells. We have shown that treatment with alum-formulated glutamic acid decarboxylase 65 (GAD-alum) preserved residual insulin secretion and induced antigen-specific responses in children with recent onset type 1 diabetes. The aim of this study was to further investigate the immunomodulatory effect of GAD-alum, focusing on CD4(+)CD25(high) cells and their association to cytokine secretion. Samples obtained 21 and 30 months after the initial injection of GAD-alum or placebo were included in the present study. GAD(65)-stimulation enhanced the percentage of CD4(+)CD25(high)FOXP3(+) cells, but reduced the percentage of CD4(+)CD25(+) cells, in samples from the GAD-alum treated group. Further, the GAD(65)-induced secretion of IL-5, -10, and -13 correlated with the expression of CD4(+)CD25(high)FOXP3(+) cells, but inversely with CD4(+)CD25(+) cells. These new data suggest that GAD-alum treatment induced GAD(65)-specific T cells with regulatory features.

Place, publisher, year, edition, pages
Elsevier Science B.V., Amsterdam, 2011
Keywords
Type 1 diabetes, Immunotherapy, GAD(65), Antigen-specific cell, FOXP3, Cytokine
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-65953 (URN)10.1016/j.clim.2010.10.004 (DOI)000286714000015 ()
Available from: 2011-02-28 Created: 2011-02-28 Last updated: 2011-02-28
Axelsson, S., Chéramy, M., Hjorth, M., Pihl, M., Åkerman, L., Martinuzzi, E., . . . Casas, R. (2011). Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes. PLoS ONE, 6(12)
Open this publication in new window or tab >>Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes
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2011 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 12Article in journal (Refereed) Published
Abstract [en]

A phase II clinical trial with glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) has shown efficacy in preserving residual insulin secretion in children and adolescents with recent-onset type 1 diabetes (T1D). We have performed a 4-year follow-up study of 59 of the original 70 patients to investigate long-term cellular and humoral immune responses after GAD-alum-treatment. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with GAD(65). Frequencies of naive, central and effector memory CD4+ and CD8+ T cells were measured, together with cytokine secretion, proliferation, gene expression and serum GAD(65) autoantibody (GADA) levels. We here show that GAD-alum-treated patients display increased memory T-cell frequencies and prompt T-cell activation upon in vitro stimulation with GAD(65), but not with control antigens, compared with placebo subjects. GAD(65)-induced T-cell activation was accompanied by secretion of T helper (Th) 1, Th2 and T regulatory cytokines and by induction of T-cell inhibitory pathways. Moreover, post-treatment serum GADA titres remained persistently increased in the GAD-alum arm, but did not inhibit GAD(65) enzymatic activity. In conclusion, memory T- and B-cell responses persist 4 years after GAD-alum-treatment. In parallel to a GAD(65)-induced T-cell activation, our results show induction of T-cell inhibitory pathways important for regulating the GAD(65) immunity.

Place, publisher, year, edition, pages
Public Library of Science, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-74156 (URN)10.1371/journal.pone.0029008 (DOI)000298366600057 ()
Note
Funding Agencies|Swedish Research Council|K2008-55x-20652-01-3|Swedish Child Diabetes Foundation (Barndiabetesfonden)||Medical Research Council of Southeast Sweden||Juvenile Diabetes Research Foundation (JDRF)|1-2008-106|Ile-de-France CODDIM||Inserm Avenir Program||Available from: 2012-01-20 Created: 2012-01-20 Last updated: 2017-12-08
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