Typing for major histocompatibility complex class II antigens in thyroid tissue blocks: association of Hashimoto's thyroiditis with HLA-DQA0301 and DQB0201 alleles.
This study was undertaken 1) to find out whether we can type major histocompatibility class II antigens from the paraffin-embedded series of thyroid tissue, and 2) to investigate whether HLA-DQ genes are involved in conferring a risk of Hashimoto's thyroiditis. To this end we used the polymerase chain reaction to amplify DNA from paraffin-embedded thyroid tissue blocks of histologically proven Hashimoto's disease. We used 46 specimens for HLA-DQA and 32 for DQB typing. The alleles were identified by sequence-specific oligonucleotide hybridizations. Fifty controls from the same geographic region were also typed using peripheral leukocyte DNA. HLA-DQA0301 (in linkage disequilibrium with DR4) was significantly increased (58.7% vs. 32% in controls; chi 2 = 6.73; P less than 0.01) in patients compared to controls. DQB0201 (in linkage disequilibrium with DR3) was also increased in the patient group (66% vs. 36% in controls; chi 2 = 6.63; P less than 0.01). Although DQA0301/DQB0201 heterozygotes (18.8%) were increased in patients compared to controls (6%), the difference was not significant. However, 81% of the patients (26 of 32) were DQA0301 and/or DQB0201 positive compared to 48% of controls (chi 2 5.98; P less than 0.05). We conclude that it is feasible to type HLA antigens from tissue blocks and that susceptibility to Hashimoto's disease is probably mediated through two pathways: DQA0301/DR4 and DQB0201/DR3.
Shi
Y
Y
Thyroid Research Laboratory, Health Sciences Centre, St. John's, Newfoundland, Canada.
Zou
M
M
Robb
D
D
Farid
N R
NR
D000483:Alleles; D001483:Base Sequence; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000032:analysis*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D000949:Histocompatibility Antigens Class II / Q000145:classification*; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012016:Reference Values; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology*
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C057615:HLA-DQbeta antigen; D000949:Histocompatibility Antigens Class II; D015345:Oligonucleotide Probes