Document Detail

Early epitope- and isotype-specific humoral immune responses to GAD65 in young children with genetic susceptibility to type 1 diabetes.
MedLine Citation:
PMID:  16990664     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: The pattern of the humoral immunity to disease-associated autoantigens may reflect the severity of the autoimmune disease process. The purpose of this study was to delineate the maturation of the humoral immunity to one of the main autoantigens in type 1 diabetes (T1D), glutamic acid decarboxylase (GAD65). DESIGN AND METHODS: Serum samples were obtained for the detection of epitope- and isotype-specific antibodies sequentially with short intervals from 36 young children with HLA-conferred genetic susceptibility to T1D starting from the first appearance of GAD65Ab. During prospective observation, ten children developed T1D. Antibodies were analyzed using biotinylated anti-human immunoglobulin (Ig) antibodies and chimeric GAD molecules in radio-binding assays. RESULTS: The immune response to GAD65 started as reactivity to the middle region and spread rapidly to the C-terminal region. IgG1 antibodies dominated among the isotypes from the first appearance of GAD65Ab, while other IgG subclasses were observed to a lesser extent. IgG4 antibodies emerged clearly as the last IgG subclass. A broad initial response comprising three to four IgG subclasses and the lack of an emerging IgG4 response during follow-up was associated with increased risk for progression to clinical diabetes (P<0.05). CONCLUSIONS: The humoral response to GAD65 epitope clusters is relatively uniform in young children, whereas there is conspicuous individual variation in IgG subclass responses except for IgG1. A narrow initial IgG subclass response to GAD65 and the emergence of IgG4 antibodies were characteristic of those who remained non-diabetic over the first few years of GAD65 autoimmunity.
Matti S Ronkainen; Sanna Hoppu; Sari Korhonen; Satu Simell; Riitta Veijola; Jorma Ilonen; Olli Simell; Mikael Knip
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of endocrinology / European Federation of Endocrine Societies     Volume:  155     ISSN:  0804-4643     ISO Abbreviation:  Eur. J. Endocrinol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-22     Completed Date:  2006-12-06     Revised Date:  2007-10-24    
Medline Journal Info:
Nlm Unique ID:  9423848     Medline TA:  Eur J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  633-42     Citation Subset:  IM    
Department of Pediatrics, University of Oulu, Oulu, Finland.
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MeSH Terms
Antibody Formation*
Antibody Specificity
Autoantibodies / blood
Child, Preschool
Diabetes Mellitus, Type 1 / blood,  genetics*,  immunology*,  prevention & control
Disease Progression
Disease-Free Survival
Epitopes / blood*
Genetic Predisposition to Disease*
Glutamate Decarboxylase / immunology*
Immunoglobulin Isotypes / blood*
Insulin / therapeutic use
Isoenzymes / immunology*
Prediabetic State / blood,  drug therapy,  immunology*
Preventive Medicine
Reg. No./Substance:
0/Autoantibodies; 0/Epitopes; 0/Immunoglobulin Isotypes; 0/Isoenzymes; 0/Placebos; 11061-68-0/Insulin; EC Decarboxylase; EC decarboxylase 2

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