Hashimoto’s Thyroiditis and HLA in Japanese*

Abstract

To investigate genetic factors involved in the pathogenesis of Hashimoto's thyroiditis (HT; goitrous autoimmune thyroiditis), HLA class I and class II antigens were analyzed in both seropositive HT (99 patients) and seronegative HT (43 patients). The frequency of HLA-DRw53 antigen was increased significantly in both seropositive HT (antigen frequency, 0.83; relative risk, 33.3; P less than 0.0002; corrected P less than 0.001) and seronegative HT (antigen frequency, 0.81; relative risk, 3.02; P less than 0.01; corrected P less than 0.05). The etiological fraction values for HLA-DRw53 in seropositive HT and seronegative HT were 0.58 and 0.54, respectively. An increased frequency of HLA-DQw4 and a decreased frequency of HLA-DQw1 were observed in patients with seronegative HT. These data suggest that susceptibility to HT is primarily associated with HLA-DRw53 and that HLA-DQ alleles may control the production of autoantibodies to the thyroid gland. The mode of inheritance of disease susceptibility for HT (controlled by a major gene in linkage disequilibrium with HLA-DRw53) was investigated by the method of Thomson and Bodmer, and it was suggested that disease susceptibility was inherited in a dominant manner.

High Prevalence of Hypothyroidism in Patients with Autoimmune Pancreatitis

“…20,21 However, the present study showed no significant association between any HLA antigens and the hypothyroid state of autoimmune pancreatitis, which suggests that the occurrence of hypothyroid state is directly correlated with autoimmune pancreatitis and not with an additional genetic background linked to the occurrence of Hashimoto's thyroiditis. In addition, AIP patients with hypothyroidism showed features atypical of Hashimoto's thyroiditis-i.e., they were preponderantly elderly males, they had no goiter, and they showed a lower prevalence of anti-TPO antibody than anti-thyroglobulin antibody.…”

“…We could find no HLA class I or II antigens for which the levels were significantly greater in hypothyroid AIP subjects than in euthyroid AIP or normal subjects, including A2, DR11, DR15, and DR53, which have been reported to be closely associated with Hashimoto's thyroiditis both in Japan and Western countries (Table 3). 20,21 Discussion Positivity for anti-Tg antibody was significantly more frequent in patients with autoimmune pancreatitis than in those with ordinary chronic pancreatitis, but there was no significant difference in the frequency of anti-TPO antibody between the two groups. It has been reported that the prevalence of autoantibodies for thyroid antigens is as high as 30% in patients with other autoimmune diseases, such as Sjoegren's syndrome 22 and systemic lupus erythematosis.…”

Genetics of autoimmune thyroid disease in the Lebanese population

“…Data on HLA haplotypes and their association with HT have been less definitive than those on GD (Vaidya et al 2002). In addition, there are no consistency between the different studies reported on HLA association with HT, such as HLA-DQw7 in English Caucasians (Tandon et al 1991), HLA-DRB1*0405 in Greek population (Kokaraki et al 2009), HLA-DRw53 in Japanese (Honda et al 1989), and HLA-DR9 in Chinese (Hawkins et al 1987). In our study, when the frequencies of HLA DQB1-DQA1 were compared between patients and controls, positive association was found with the haplotypes DQB1*0302-DQA1*0501 (P 00.008, OR 02.378, CI 0 1.241-4.558) and DQB1*0302-DQA1*0301 (P 00.002,OR02.402,.…”

Hyperthyroid Graves' Disease and Primary Hypothyroidism Caused by TSH Receptor Antibodies in Monozygotic Twins: Case Reports.

“…Associations between some HLA antigens and autoimmune thyroid diseases have consistently been observed [5,16,[18][19][20][21][22][23][24].…”

“…Those associated with Hashimoto's disease include A2, DR2, DR3, DQ7, DRB4*0101, DQA 1 *0102 and DQB 1 *0602 [16,21]. In Japanese patients with high TSBAb activity the HLA antigens include B35, B67, Bw60 and Dw 8 [16,17].…”