LiU Electronic Press
Download:
File size:
1893 kb
Format:
application/pdf
Author:
Axelsson, Stina (Linköping University, Department of Clinical and Experimental Medicine, Pediatrics) (Linköping University, Faculty of Health Sciences)
Chéramy, Mikael (Linköping University, Department of Clinical and Experimental Medicine, Pediatrics) (Linköping University, Faculty of Health Sciences)
Hjorth, Maria (Linköping University, Department of Clinical and Experimental Medicine, Pediatrics) (Linköping University, Faculty of Health Sciences)
Pihl, Mikael (Linköping University, Department of Clinical and Experimental Medicine, Pediatrics) (Linköping University, Faculty of Health Sciences)
Åkerman, Linda (Linköping University, Department of Clinical and Experimental Medicine, Pediatrics) (Linköping University, Faculty of Health Sciences)
Martinuzzi, Emanuela ( St Vincent de Paul Hospital)
Mallone, Roberto ( St Vincent de Paul Hospital)
Ludvigsson, Johnny (Linköping University, Department of Clinical and Experimental Medicine, Pediatrics) (Linköping University, Faculty of Health Sciences) (Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping)
Casas, Rosaura (Linköping University, Department of Clinical and Experimental Medicine, Pediatrics) (Linköping University, Faculty of Health Sciences)
Title:
Long-Lasting Immune Responses 4 Years after GAD-Alum Treatment in Children with Type 1 Diabetes
Department:
Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping
Linköping University, Faculty of Health Sciences
Linköping University, Department of Clinical and Experimental Medicine, Pediatrics
Publication type:
Article in journal (Refereed)
Language:
English
Publisher: Public Library of Science
Status:
Published
In:
PLoS ONE(ISSN 1932-6203)
Volume:
6
Issue:
12
Year of publ.:
2011
URI:
urn:nbn:se:liu:diva-74156
Permanent link:
http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-74156
ISI:
000298366600057
Subject category:
Medical and Health Sciences
SVEP category:
MEDICINE
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.

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:
2012-10-24
Statistics:
80 hits
FILE INFORMATION
File size:
1893 kb
Mimetype:
application/pdf
Type:
fulltext
Statistics:
140 hits
Version:
Publisherʼs version