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Schmid, S.* ; Molteni, A.* ; Füchtenbusch, M.* ; Naserke, H.E.* ; Ziegler, A.-G.* ; Bonifacio, E.*

Reduced il-4 associated immune responses in early pre-diabetes.

Diabetologia 45, 677-685 (2002)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Aims/hypothesis. The aim of this study was to determine whether beta-cell autoimmunity is associated with immune response bias to exogenous antigens. Methods. IgG subclass responses against tetanus toxoid and rubella were measured after vaccination in children with (n=36) and without (n=73) islet autoantibodies participating in the BABYDIAB prospective study of offspring of parents with Type I (insulin-dependent) diabetes mellitus. All children had been vaccinated against tetanus toxoid antigen before 6 months of age and at 18 months of age, and against live attenuated rubella virus at 18 months of age and again before 5 years of age. Tetanus toxoid specific IgG subclasses and cytokine responses were compared in a second cohort of subjects. Results. Responses to tetanus toxoid in islet-autoantibody-negative children were characterized by early IgG1 antibodies at 9 months of age followed by the appearance of IgG4 and lesser IgG2 antibodies at 2 years of age. Children who had developed islet autoimmunity before one year of age (n=15) did not have the shift to IgG4 and IgG2 anti-TT after booster vaccination (p<0.01), and had undetectable or IgG1 restricted responses. This defect was independent of HLA class II genotype, was restricted to children who had islet autoimmunity before 1 year of age, and was most evident in children who already had multiple islet autoantibodies by 9 months of age. IgG4 and IgG2 anti-TT correlated with IL-4 (p<0.005), but not IFNγ responses. Antibody responses to the IFNγ-inducing rubella vaccination were strongly IgG1 dominated and no differences were observed between islet autoantibody positive and negative children. Conclusions/interpretation. These data are consistent with a reduced capacity to make IL-4 promoted antibody responses to exogenous antigen in early pre-diabetes.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 0012-186X
e-ISSN 1432-0428
Journal Diabetologia
Quellenangaben Volume: 45, Issue: 5, Pages: 677-685 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Berlin ; Heidelberg [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Institute of Diabetes and Obesity (IDO)
Institute of Pancreatic Islet Research (IPI)