Relation among mannose-binding lectin 2 genotype, beta-cell autoantibodies, and risk for type 1 diabetes in Finnish children.
Mannose-binding lectin (MBL) is a key mediator of innate immunity, the insufficiency of which is caused by point mutations in the MBL2 gene. MBL insufficiency is associated with increased susceptibility to infections and certain autoimmune diseases, but its impact in the pathogenesis and risk of type 1 diabetes (T1D) is controversial. We investigated the significance of the MBL2 genotype on the risk of T1D in a Finnish study population comprising 470 diabetic children and 501 controls. Furthermore, the effect of MBL2 gene polymorphism on the emergence of beta-cell autoantibodies in 289 unaffected children with human leukocyte antigen-conferred susceptibility to T1D was assessed. MBL genotype had no significant effect on the risk or onset age of T1D. However, children with the biallelic variant genotype reflecting total MBL deficiency tested positive more frequently for > or =3 autoantibodies compared with children with another genotype (odds ratio = 6.0, 95% confidence interval 1.3-28; p = 0.013). In conclusion, the MBL2 genotype did not affect susceptibility to T1D in children, and this finding does not support previous reports implicating a role of the MBL2 genotype as a factor predisposing to T1D. The association of the biallelic variant genotype with positivity for multiple autoantibodies suggests that intermolecular epitope spreading may be linked with impaired clearance of autoantigens as a result of MBL deficiency.
Aittoniemi
J
J
Department of Clinical Microbiology, Centre for Laboratory Medicine, Pirkanmaa Hospital District, Tampere, Finland. janne.aittoniemi@pshp.fi <janne.aittoniemi@pshp.fi>
Turpeinen
H
H
Tiittanen
M
M
Knip
M
M
Simell
O
O
Ilonen
J
J
Vaarala
O
O
D000293:Adolescent; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D005387:Finland; D005838:Genotype; D006683:HLA-DQ Antigens / Q000276:immunology; D006801:Humans; D007223:Infant; D050417:Insulin-Secreting Cells / Q000276:immunology*; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D001323:Autoantibodies; D001324:Autoantigens; D006683:HLA-DQ Antigens; C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin