한국인 자가면역성 갑상선질환에 있어서의 HLA항원분포에 관한 연구

Abstract

[한글]

1969년 McDevitt와 Benacerraf에 의해 면역반응을 지배하는 일련의 유전인자가 주요 조직적합군(major histocompatibility complex)에 있음이 밝혀진 후 HLA항원과 질병, 특히 자가면역성 질환과의 관계를 규명하는 연구가 진행되었다. 주요 조직적합군과 질병과의 연관성에 대한 연구는 질병의 진단과 예후 및 질병의 진행과정 등을 이해하는데 도움을 주며 특히 강직성 척추염은 HLA-B27, 중증 근무력증 및 만성 활동성 간염은 HLA-B8, 인슐린 의존성 당뇨병 및 전신성 홍반성 낭창은 HLA-B8 및 Bw15와 밀접한 관계가 있다고 보고되었다.

자가면역성 갑상선 질환의 원인은 자가면역기전과 유전적 요소가 중요한 역할을 하기 때문에 HLA항원 분포와의 연관성을 규명하는 것은 매우 흥미있는 연구가 될 것이다. 또한 질병에 대한 감수성과 관련된 HLA항원 분포는 종족마다 특이한 차이가 있는 것으로 알려져 있으며 Graves 씨병에 있어서 백인은 HLA-B8 및 -DR3(Grumet 등, 1974;Farid 등, 1980b).

일본인은 HLA-Bw35 (Grumet 등, 1975;Nakao 등, 1977)가 의의있게 증가되었다는 보고가 있다.

이에 저자는 한국인 자가면역성 갑상선질환인 Graves씨병 환자 97예와 Hashimoto 씨병 환자 37예에서 HLA-A, -B 및 -C 항원 검사를 시행하였고, HLA-DR항원 검사는 이들 중 Graves씨병 환자 79예 그리고 Hashimoto 씨병 환자 33예에 시행하였으며 정상 대조군은 건강하고 서로 혈연관계가 없는 한국인 100예에서 HLA-A, -B 및 -C 항원검사와 50예에서 HLA-DR 항원검사를 실시하여 다음과 같은 결과를 얻었다.

1. Graves 씨병 환자군과 정상대조군과의 HLA-A 항원 빈도를 비교 관찰하여 보면 A11이 Graves 씨병 환자군에서 29.9%로 정상대조군의 15%에 비해 유의(p<0.025)한 증가를 보였고 A10은 Graves 씨병 환자군에서 10.3%로서 대조군에서의 22%에 비하여 유의(p<0.05)한

감소를 보였다.

Hashimoto 씨병 환자군에서 A2는 67.6%로서 정상대조군에서의 43%에 비하여 의의있게 증가되었다(p<0.05).

2. HLA-B항원의 분포를 보면 Graves 씨병 환자군에서 B12는 4.1%로 정상대조군의 13%에 비하여 의의있게 (p<0.05) 감소되어 있었다.

3. HLA-C 항원은 Cw3가 Graves 씨병 및 Hashimoto 씨병 환자군에서 정상대조군에 비하여 증가되었고 Cw4와 Cw5가 감소된 경향을 보였으나 통계적인 의의는 없었다.

4. HLA-DR 항원은 DRw8이 Graves 씨병 및 Hashimoto 씨병 환자군에서 각각 35.4% (p<0.01) 및 42.4%(p<0.005)로 정상대조군의 12%보다 유의하게 증가되었고 HLA-DRw6y 항원 빈도는 정상대조군에서 48% Hashimoto 씨병 환자군은 24.2%로 통계학적으로 의의있게 감소되어 있었다(p<0.05).

이상의 결과를 요약하면 Graves 씨병 환자군에서는 대조군에 비해 HLA-A11 및 DRw8이 유의하게 증가된 반면 HLA-A10 및 B12는 유의하게 감소되어 있었고, Hashimoto 씨병 환자군에서는 HLA-A2와 DRw8이 의의있게 증가되어 있었다.

[영문]

Since McDevitt and Benacerraf first discovered a series of genes that governed immune response and these genes were located in the major histocompatibility locus, many investigators had examined the associations of the HLA antigens and susceptibility to certain diseases, especially those associated with autoimmunity.

The study of an association between HLA alleles and diseases is of predictive value in the diagnosis and outcome of therapy. In white populations, HLA-B8 has been reported to be associated with autoimmune diseases such as celiac disease, active chronic hepatitis, myasthenia gravis, insulin-dependent diabetes mellitus

and idiopathic Addison's disease. Because autoimmunity appears to be a characteristic feature of autoimmune thyroid disease, and also because an animal model exists linking experimentally induced murine thyroiditis and the mouse major histocompatibility locus, autoimmune thyroiditis and the mouse major histocompatibility locus, autoimmune thyroid disease appeared to be particularly interesting disorder to investigate any HLA antigen associations. Specific allelic associations with a particular disease very among ethnic groups. Graves' disease was reported to be associated with HLA-B8 and -DR3 in Caucasian patients, HLA-BW35 in Japanese patients and HLA-Bw46 in Chinese patients. The present study was undertaken to investigate the associated between HLA and autoimmune thyroid disease in Korean.

HLA-A, -B and -C antigens were determined in 97 unrelated patients with Graves' disease, 37 unrelated patients with Hashimoto's disease and 100 unrelated control. HLA-DR antigens were determined 79 unrelated patients with Graves' diseage, 33

unrelated patients with Hashimoto's disease and 50 unrelated control. Diagnosis was based on clinical features, thyroid hormone level, radioactive 131 I uptake with scan, thyroid autoantibodies and histopathologic findings.

Serum T3 and T4 were measured by polyethlene glycol radioimmunoassay and TSH by double antibody radioimmunoassay. Thyroid autoantibodies to thyroblobulin and microsomes were measured by the tanned sheep erythrocyte hemaeglutination technique using commercial test kits.

1. The frequency of HLA-All was significantly increased (P<0.025: relative risk 2.4) in patients with Graves' disease (29.9%) as compared with controls (15%) and HLA-10 is decreased in patients with Graves' disease (P<0.05). The frequency of

HLA-A2 was significantly increased (P<0.025) in patients with Hashimoto's disease (67.6%) as compared with controls (43%).

2. The frequency of HLA-B12 was decreased (P<0.05) in patients with Graves' disease.

No significant differences on the frequency of HLA-B antigens between those with Hashimoto's disease and controls were found.

3. HLA-Cw3 was increased, and HLA-Cw4 and -Cw5 decreased in patients with Graves' or Hashimoto's disease as compared with controls but the P value was not significant.

4. The frequency of HLA-DRw8 was increased in patients with Graves' disease (35.4% P<0.01) and Hashimoto's disease (42.4% P<0.005) as compared with controls (12%). HLA-DRw6y was decreased in patients with Hashimoto's disease as compared with controls(P<0.05).

In conclusion, frequency of HLA-B antigens which are significantly increased in other races are not increased in Korean patients with autoimmune thyroid disease, but HLA-DRw8 is significantly increased in our patients.