Cord blood islet autoantibodies and seasonal association with the type 1 diabetes high-risk genotype.
OBJECTIVE
Human leukocyte antigen DQ (HLA-DQ) genetic factors and islet autoantibodies are strongly associated with type 1 diabetes (T1D) and are currently used to predict T1D. This study examined whether islet autoantibodies in the cord blood of newborns to nondiabetic mothers were associated with the (T1D) high-risk genotype HLA-DQ2/8, gestational infections or both.


METHODS
Cord blood samples were taken from 33 683 newborns and used for HLA typing and analyses of islet autoantibodies. Parents completed questionnaires when the child was 2 months of age.


RESULTS
The prevalence of newborn islet autoantibodies consistently varied with season over 4 years (P<0.0001); lowest in first quarter (1.2%) and highest in third (2.4%). Cord blood islet autoantibodies were associated with HLA-DQ2/8 in the second (OR, 2.30; P=0.02), third (OR, 2.12; P=0.008) and fourth quarters (OR, 2.49; P=0.007), but not in the first (OR, 1.13). Reported gastroenteritis was additionally associated with islet autoantibodies in the third quarter (OR, 1.80, P=0.04).


CONCLUSIONS
An association between HLA and islet autoimmunity may depend on environmental exposure during pregnancy. Follow-up of mothers and children will determine risk of T1D.
Lynch
K F
KF
Department of Clinical Sciences, University Hospital MAS, Lund University, Malmö, Sweden. kristian.lynch@med.lu.se
Lernmark
B
B
Merlo
J
J
Cilio
C M
CM
Ivarsson
S-A
SA
Lernmark
A
A
D001323:Autoantibodies / Q000276:immunology*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D004781:Environmental Exposure; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005759:Gastroenteritis / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology; D016017:Odds Ratio; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D011254:Pregnancy in Diabetics / Q000235:genetics / Q000276:immunology; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D012621:Seasons
D001323:Autoantibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C516862:PTPRN protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2