Journal
CLINICAL IMMUNOLOGY
Volume 137, Issue 1, Pages 31-40Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2010.06.001
Keywords
Immunotherapy; GAD(65); GAD-alum; GADA; Type 1 diabetes; T1D; IgG; IgG subclass
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Funding
- Swedish Research Council [K2008-55x-20652-01-3]
- Swedish Child Diabetes Foundation (Barndiabetesfonden)
- Medical Research Council of Southeast Sweden
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We have previously shown that two injections of 20 mu g GAD-alum to recent onset type 1 diabetic children induced GADA levels in parallel to preservation of insulin secretion. Here we investigated if boosted GADA induced changes in IgG1, 2, 3 and 4 subclass distributions or affected GAD(65) enzyme activity. We further studied the specific effect of GAD-alum through analyses of IA-2A, tetanus toxoid and total IgE antibodies. Serum from children receiving GAD alum or placebo was collected pre-treatment and after 3, 9, 15 and 21 months. At 3 months a reduced percentage of IgG1 and increased IgG3/IgG4 were detected in GAD-alum treated. Further, IA-2A, IgE and tetanus toxoid antibodies, as well as GAD(65) enzyme activity, were unaffected confirming the specific effect of treatment. In the GAD-alum group, higher pretreatment GADA were associated to more pronounced C-peptide preservation. The induced IgG3/IgG4 and reduced IgG1 suggest a Th2 deviation of the immune response. (C) 2010 Elsevier Inc. All rights reserved.
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