Reduced IL-4 associated antibody responses to vaccine in early pre-diabetes.
OBJECTIVE
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 IFNgamma responses. Antibody responses to the IFNgamma-inducing rubella vaccination were strongly IgG1 dominated and no differences were observed between islet autoantibody positive and negative children.


CONCLUSIONS
These data are consistent with a reduced capacity to make IL-4 promoted antibody responses to exogenous antigen in early pre-diabetes.
Schmid
S
S
Diabetes Research Institute and 3rd Medical Department, München-Schwabing Hospital, Germany.
Molteni
A
A
Füchtenbusch
M
M
Naserke
H E
HE
Ziegler
A-G
AG
Bonifacio
E
E
D000375:Aging; D000917:Antibody Formation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D015847:Interleukin-4 / Q000276:immunology*; D008297:Male; D010290:Parents; D011236:Prediabetic State / Q000276:immunology*; D012411:Rubella Vaccine; D013745:Tetanus Toxoid / Q000276:immunology*; D014613:Vaccines, Attenuated
D007074:Immunoglobulin G; D012411:Rubella Vaccine; D013745:Tetanus Toxoid; D014613:Vaccines, Attenuated; D015847:Interleukin-4