Signs of beta-cell autoimmunity and HLA-defined diabetes susceptibility in the Finnish population: the sib cohort from the Type 1 Diabetes Prediction and Prevention Study.
OBJECTIVE
To assess the role of HLA-defined genetic diabetes susceptibility in the appearance of signs of beta-cell autoimmunity in a series of children derived from the general population.


METHODS
Tests for five HLA DQB1 alleles and four diabetes-associated autoantibodies were carried out on 1,584 older sibs of infants with an increased HLA-defined genetic risk of Type 1 diabetes. The DQB1 genotypes were classified into those conferring high (* 02/0302), moderate (* 0302/x; where x indicates * 0302 or a non-defined allele), low (* 0301/0302, * 02/0301, * 02/x, * 0302/0602, * 0302/0603; where x indicates * 02 or a non-defined allele) or decreased risk (other genotypes).


RESULTS
Both islet cell antibodies (ICA) and GAD65 antibodies (GADA) were more frequent among the sibs with the high-risk genotype than among those with a low or decreased risk. Insulin autoantibodies and IA-2 antibodies (IA-2A) were more prevalent in the high-risk than low-risk sibs. Sibs with moderate-risk genotypes tested positive for ICA, GADA and IA-2A more often than sibs with genotypes conferring decreased risk. Autoantibody titres were also dependent on the genetic risk with high risk sibs having the highest values. Sibs carrying high-risk or moderate-risk genotypes tested positive for multiple antibodies (> or =2) more often than did the sibs with low or decreased genetic risk.


CONCLUSIONS
The data show that HLA-defined susceptibility to Type 1 diabetes has an effect on both the quality and quantity of humoral beta-cell autoimmunity in unaffected children derived from the general population.
Kukko
M
M
Medical School, University of Tampere, and Department of Paediatrics, Tampere University Hospital, Tampere, Finland. mikael.knip@hus.fi
Kimpimäki
T
T
Kupila
A
A
Korhonen
S
S
Kulmala
P
P
Savola
K
K
Simell
T
T
Keskinen
P
P
Ilonen
J
J
Simell
O
O
Knip
M
M
D000906:Antibodies / Q000032:analysis; D001323:Autoantibodies / Q000032:analysis; D015551:Autoimmunity; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D007527:Isoenzymes / Q000276:immunology; D008297:Male; D011379:Prognosis
D000906:Antibodies; D001323:Autoantibodies; D006680:HLA Antigens; C096322:ICA512 autoantibody; D007328:Insulin; D007527:Isoenzymes; C024211:islet cell antibody; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2