SUSCEPTIBILITY AND RESISTANCE ALLELES OF HUMAN-LEUKOCYTE ANTIGEN (HLA) DQA1 AND HLA DQB1 ARE SHARED IN ENDOCRINE AUTOIMMUNE-DISEASE

Because particular human leukocyte antigen (HLA) DQ alleles are the ma jor predisposing Factors for type 1 diabetes mellitus (IDDM), we inves tigated whether they are shared by other endocrine autoimmune diseases . We, therefore, analyzed the HLA DQ genotypes of 171 patients with ID DM, 271 with Graves' disease (GD), 65 with Hashimoto's thyroiditis, 51 with postpartum thyroiditis, 53 with Addison's disease (AD), and 271 healthy controls. HLA DQA1 and DQB1 alleles were defined by polymerase chain reaction and sequence-specific oligonucleotide hybridization as well as by single strand conformational polymorphism analysis. HLA DQ A10501 was significantly more frequent in IDDM (60%), GD (65%), and A D (70%) than in controls (43%); DQA10301 was significantly more frequ ent only in IDDM (67% vs. 30% controls). The heterozygous state DQA10 301/0501 was found in 9% of controls and 35% of IDDM (relative risk, 5.6) arginine at position 52 on either DQA1 allele was significantly m ore frequent in patients with IDDM (94%), GD (80%), and AD (89%) compa red with controls (66%). HLA DQB10201 and DQB1*0302 were more frequen t in IDDM patients (0201, 62% vs. 36% in controls; *0302, 59% vs. 19% controls), whereas DQB10602 was less Frequent in IDDM (4%) and GD (1 8% vs. 31% of controls). In conclusion, endocrine autoimmunity has a c ommon immunogenetic background; susceptibility is conferred by DQA105 01 as well as an arginine at position 52 of DQA1 alleles, and protecti on against IDDM and GD is conferred by DQB10602.