The risk of developing factor VIII inhibitor antibodies in haemophilia A may relate both to factor VIII genotype and genes within the HLA complex known to influence immune response.
We investigated a cohort of 176 patients with severe haemophilia A and with either high-level inhibitors (>10BU/ml) or with no history of an inhibitor, stratified according to the presence or absence of the factor VIII gene intron 22 inversion.
HLA DRB 1, DQAI and DQB I polymorphisms were determined by PCR.
HLA frequencies from 137 United Kingdom controls were used for comparison.
HLA phenotype frequency differences, expressed as odds ratios with 95% confidence intervals were as follows : HLA-DRB*1501, DQBl*0602 and DQA1*0102 were all increased in frequency in patients with inhibitors, only DQA1 *0102 reaching statistical significance (OR 2.7,1.2-5.9).
These alleles form part of an established HLA haplotype.
The frequencies of HLA-DRB1*1501, DQB1*0602 and DQA1 *0102 were particularly raised in patients with inhibitors and a factor VIII gene intron 22 inversion, although again only DQA1*0102 achieved significance (OR 3.1,1.0-10.1).
The frequency of DRB1*01, DQB1*0501, DQA1*0101 were also increased in inhibitor patients lacking the intron 22 inversion although this failed to achieve statistical significance.
This data suggests that HLA class II profile constitutes a weak risk factor for developing inhibitor antibodies to factor VIII. (...)
Mots-clés Pascal : Hémophilie A, Antigène histocompatibilité classe II, Système HLA, Système histocompatibilité majeur, Phénotype, Inhibiteur, Facteur antihémophilique A, Facteur coagulation, Anticorps, Facteur risque, Epidémiologie, Royaume Uni, Europe, Homme, Hémopathie, Coagulopathie, Maladie héréditaire
Mots-clés Pascal anglais : Hemophilia A, Class II histocompatibility antigen, HLA-System, Major histocompatibility system, Phenotype, Inhibitor, Factor VIII, Coagulation factor, Antibody, Risk factor, Epidemiology, United Kingdom, Europe, Human, Hemopathy, Coagulopathy, Genetic disease
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 97-0160310
Code Inist : 002B19C. Création : 21/05/1997.