A STRONG ASSOCIATION BETWEEN THYROTROPIN RECEPTOR-BLOCKING ANTIBODY-POSITIVE ATROPHIC AUTOIMMUNE-THYROIDITIS AND HLA-DR8 AND HLA-DQB1-ASTERISK-0302 IN KOREANS

We investigated whether the associations between HLA alleles of patien ts with autoimmune hypothyroidism varied according to the presence or absence of TSH receptor-blocking antibody (TRBab). We analyzed the HLA -A, -B, -C, and -DR antigens by serotyping and the DQA1 and DQB1 genes using both enzymatic DNA amplification and sequence-specific oligonuc leotide hybridizations. The patient population consisted of 47 Korean patients with atrophic autoimmune thyroiditis and 62 patients with goi trous autoimmune thyroiditis. The antigen frequency of HLA-DR8 was sig nificantly increased in 23 atrophic autoimmune thyroiditis patients th at were positive for TSH binding inhibitor immunoglobulin (TBII) compa red to 136 controls [52% vs. 16%; chi2 = 13.1; Pc (corrected P value) = 0.003]. This relative risk was 5.7; the etiological fraction was 0.4 3. HLA-DQB10302 was also increased in patients with TBII-positive atr ophic autoimmune thyroiditis (24% vs. 7%; chi2 = 11.2; Pc = 0.012; rel ative risk = 4.4; etiological fraction = 0.19). No specific DR antigen s or DQB1 alleles were increased in either TBII-negative atrophic auto immune thyroiditis or goitrous autoimmune thyroiditis. A significant d ecrease in the frequency of HLA-DR6 antigen was observed in both TBII- positive atrophic autoimmune thyroiditis (0% vs. 32%; chi2 = 8.4; Pc = 0.03) and goitrous autoimmune thyroiditis (0% vs. 32%; chi2 = 23.2; P c < 0.001) patients. The frequency of the HLA-Cw1 antigen was signific antly increased in all patient groups. We conclude that TRBab-positive atrophic autoimmune thyroiditis is immunogenetically different from b oth goitrous autoimmune thyroiditis and TRBab-negative atrophic autoim mune thyroiditis. It is possible that HLA-DR8 and/or DQB10302 may be related to the susceptibility genes involved in the production of TRBa b in Koreans.