Long-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes.

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...

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Autores principales:	Stina Axelsson, Mikael Chéramy, Maria Hjorth, Mikael Pihl, Linda Akerman, Emanuela Martinuzzi, Roberto Mallone, Johnny Ludvigsson, Rosaura Casas
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7beb2246337149e8b59df7e8f7bc3c5c
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spelling	oai:doaj.org-article:7beb2246337149e8b59df7e8f7bc3c5c2021-11-18T07:32:29ZLong-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes.1932-620310.1371/journal.pone.0029008https://doaj.org/article/7beb2246337149e8b59df7e8f7bc3c5c2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174945/?tool=EBIhttps://doaj.org/toc/1932-6203A 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 naïve, 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.Stina AxelssonMikael ChéramyMaria HjorthMikael PihlLinda AkermanEmanuela MartinuzziRoberto MalloneJohnny LudvigssonRosaura CasasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e29008 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stina Axelsson Mikael Chéramy Maria Hjorth Mikael Pihl Linda Akerman Emanuela Martinuzzi Roberto Mallone Johnny Ludvigsson Rosaura Casas Long-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes.
description	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 naïve, 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.
format	article
author	Stina Axelsson Mikael Chéramy Maria Hjorth Mikael Pihl Linda Akerman Emanuela Martinuzzi Roberto Mallone Johnny Ludvigsson Rosaura Casas
author_facet	Stina Axelsson Mikael Chéramy Maria Hjorth Mikael Pihl Linda Akerman Emanuela Martinuzzi Roberto Mallone Johnny Ludvigsson Rosaura Casas
author_sort	Stina Axelsson
title	Long-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes.
title_short	Long-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes.
title_full	Long-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes.
title_fullStr	Long-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes.
title_full_unstemmed	Long-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes.
title_sort	long-lasting immune responses 4 years after gad-alum treatment in children with type 1 diabetes.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/7beb2246337149e8b59df7e8f7bc3c5c
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Long-lasting immune responses 4 years after GAD-alum treatment in children with type 1 diabetes.

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