GAD-alum treatment in patients with type 1 diabetes and the subsequent effect on GADA IgG subclass distribution, GAD65 enzyme activity and humoral response

被引:36
作者
Cheramy, Mikael [1 ,2 ]
Skoglund, Camilla [1 ,2 ]
Johansson, Ingela [1 ,2 ]
Ludvigsson, Johnny [1 ,2 ]
Hampe, Christiane S. [3 ]
Casas, Rosaura [1 ,2 ]
机构
[1] Linkoping Univ, Div Paediat, Dept Clin & Expt Med, S-58185 Linkoping, Sweden
[2] Linkoping Univ, Dept Clin & Expt Med, Diabet Res Ctr, S-58185 Linkoping, Sweden
[3] Univ Washington, Dept Med, Seattle, WA USA
基金
瑞典研究理事会; 英国医学研究理事会;
关键词
Immunotherapy; GAD(65); GAD-alum; GADA; Type; 1; diabetes; T1D; IgG; IgG subclass; GLUTAMIC-ACID DECARBOXYLASE; STIFF-PERSON-SYNDROME; BETA-CELL FUNCTION; IMMUNE-RESPONSES; C-PEPTIDE; INSULIN; ONSET; ANTIBODIES; MELLITUS; AUTOANTIBODIES;
D O I
10.1016/j.clim.2010.06.001
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:31 / 40
页数:10
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