Behcet 증후군 환자에서 항 인지질 항체인 항 Cardiolipin 항체 및 루푸스성 항 응고인자 측정에 관한 연구

Abstract

[한글]

Behcet증후군은 재발성 구강 및 외음부 궤양, 피부병변, 포도막염과 같은 안질환의 주 증상들과 함께 환절염, 심맥관계 및 중추신경계등의 증상을 보이는 질환이다. 발병기전에 대해서는 여러가지로 논의가 있었으나 특히 면역학적 측면이 최근 활발히 연구되고 있다

. 연구자는 Behcet증후군의 면역학적 연구의 일환으로 혈청내 존재하는 자가항체인 항인지질 항체 중 항Cardiolipin항체 및 루푸스성 항응고인자의 양성도를 파악하고 양성을 보이는 환자에서 혈관, 혈액학적 및 면역학적 변화를 관찰하고자 하였다.

연구대상온 연세대학교 의과대학 세브란스병원 Behcet증후군 특수진료소에 내원하여 Behcet증후군으로 진단받은 환자 91명으로 하였다. 이중 68명에서 항Cardiolipin 항체를 ELISA방법에 의해 측정하였고, 69명에서 루푸스성 항응고인자를 Kaolin cloning time법으로 측정하여 다음과 같은 결과를 얻었다.

1. Behcet증후군 환자 혈청내에는 정상인에서 보다 항Cardiolipin 항체가 놓은 빈도로 검출되었으며(P<7.05) 특히 IgM isotype이 의의있게 높은 빈도로 검출되었다(P<0.01). 그러나 egG isotype은 정상건강인과 뚜렷한 차이가 없었다. 루푸스성 항응고인자는 정상인

에서 검출되지 않았고 Behcet증후군 환자에서는 4%에서 검출 되었다.

2. 항 Cardiolipin 항체와 루푸스성 항응고인자는 모두 성별이나 나이에 따른 뚜렷한 차이가 없었다.

3. Shimizu의 분류 아령별로는 완전형 60%(15예중 9예),불완전형 47%(32예중 15예),용의형 25%(12예중 3예)의 순이었으며 가능형에서는 항Cardiolipin 항체가 검출되지 않았다. 루푸스성 항 응고인자는 불완전형에서 8%,용의형에서 6%로 검출되었고 그외 분류 아형

에서는 루푸스성 항응고인자가 검출되지 앉았다.

4. Lehiu의 분류 아형별로는 신경형 100%(1예중 1예),점막피부형 86%(29예중 25예),안형 77%(26예중 20예), 관절형 75%,(12예중 9예)의 순으로 항Cardiolipin 항체가 검출되었으며 루푸스성 항 옹고인자는 신경형을 제외한 모든 분류 아형에서 3-8%로 검출되었다.

5.검사당시 나타난 임상증상수에 따라서는 검사당시 임상증상수가 2개이상인 경우에만 항Cardiolipin 항체가 검출되었고 루푸스성 항응고인자는 임상증상수가 3개이상인 경우에 만 루푸스성 항 응고인자가 검출되 었다. 그러나 항Cardiolipin 항체나 루푸스성 항응고인자의 검출과 질병의 활성도에 따른 뚜렷한 차이는 없었다.

6. 루푸스성 항응고인자가 검출되는경우 항Cardiolipin 항체는 100%에서 검출되었고 특히 isotype은 모두 IgM이었다. 루푸스성 항 응고인자가 검출되지 않는 경우 항 Cardiolipin 항체는 86%에서 검출되었다.

7. 혈관내 혈전은 항 Cardiolipin항체가 검출되는 환자의 23%에서 관찰되었으며 isotope은 모두 IgM으로 관찰되었다. 루푸스성 항응고인자가 검출되는 환자의 경우 혈관내 혈전이 관찰되지 않았다.

이상의 결과는 Behcet증후군환자 혈청내에는 항Cardiolipin항체가 출현할수 있음을 제시하고 있으나 이들이 질병의 활성도나 혈전형성과의 관계가 없는 것으로 밝혀져 향후 Behcet증후군의 병인론에서 항Cardiolipin항체 출현의 의미를 밝히기 위해서는 계속적인 연구가 필요할 것으로 생각된다.

Anticardiollpin Antibodies and Lupus Anticoagulants in Behcet's Disease

Hye Goo Ji

Department of Medical Science The Graduate School, Yonsei University

(Directed by Assistant Professor Dongsik Bang,M.D.)

Although Behcet's syndrome is found all over the world, certain geographic

predilections do exist ,most cases of Behcet's syndrome have been reported in the

eastern Mediterranean countries and the Far East.

The etiology of Behcet's syndrome romaines an enigma, and there has been no

unifying hypothesis to explain the underlying pathogenetic abnormalities observed

in this disease. Nevertheless, there is significant evidence to suggest that

endothelial cell injury modulated by enhanced PMN activity, increased release of

neutrophil-derived oxygen intermediates, and production of anticardiolipin

antibodies all play a pathogenetic role in the development of the complications of

Behcet's syndrome To date there is no direct in-vivo evidence that Ihe

antiphopholipid antibody is pathogenetic. However, there is conflicting in-vitro

evidence, that antiphospholipid antibodies may indeed play a part in the disease

process. The present study was performed to determine the presence of

antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulants)

in our patients with Behcet's syndrome in relation to clinical type, clinical

activity and thrombosis.

Followings are the results summarized:

1. Higher than normal anticardiolipin antibody titer was found with high

frequency (P<0.05); particularly significant was the high frequency with which IgM

isotype was found (P<0.0l). There was no significant difference in IgG isotype

titer compared to a normal healthy person. Lupus anticoagulant was not found in a

normal person but was found in 4% of Behect's syndrome patients.

2. There was no significant difference between the anticardiolipin antibody and

the lupus anticoagulant in regard to sex and age.

3. In adherence to Shimizu's classification, the percentage of anticardiolipin

antibody found is as fellows; 60%(9 in 15) in the complete type,47%(15 in32)in the

incomplete type, 25%(3 in 12) in the suspected type, and no antibody was found in

the possible type. The percentage of lupus anticoagulants found is 8% in the

incomplete type,6% in the suspected type and not found in other types.

In adherence to Lehner's classification, the percentage of anticardiolipin

antibody found is as follows; 100%(1 in 1) in the neurological type, 86%(25in 29)

in the mucocutaneous type,75%(20 in 26) in the arthritic type, and in the case of

lupus anticoagulants, 3-8% is found in all types except the neurological type.

5. The number of clinical symptoms found at the time of the test was more than 2

in the case of anticardiolipin antibody positive and more than 3 in the case of

lupus anticoagulant positive. However, there was no significant statistical

difference between the level of anticardiolipin antibody and lupus anticoagulant

and the activity of disease.

6. In a1l of the cases, when a lupus anticoagulant was found, anlicardiolipin

antibody was also found, and the isotype was always IgM. When a lupus anticoagulant

was not found, anticardiolipin antibody was found in 86% of the cases.

7. Intravascular thrombosis was found in 23% of the patients with positive

anticardiolipin antibody and the isotype was always IgM. In the case of a lupus

anticoagulant positive patients intravascular thrombosis was not found.

[영문]

Although Behcet's syndrome is found all over the world, certain geographic predilections do exist ,most cases of Behcet's syndrome have been reported in the eastern Mediterranean countries and the Far East.

The etiology of Behcet's syndrome romaines an enigma, and there has been no unifying hypothesis to explain the underlying pathogenetic abnormalities observed in this disease. Nevertheless, there is significant evidence to suggest that

endothelial cell injury modulated by enhanced PMN activity, increased release of neutrophil-derived oxygen intermediates, and production of anticardiolipin antibodies all play a pathogenetic role in the development of the complications of Behcet's syndrome To date there is no direct in-vivo evidence that Ihe

antiphopholipid antibody is pathogenetic. However, there is conflicting in-vitro evidence, that antiphospholipid antibodies may indeed play a part in the disease process. The present study was performed to determine the presence of antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulants)

in our patients with Behcet's syndrome in relation to clinical type, clinical activity and thrombosis.

Followings are the results summarized:

1. Higher than normal anticardiolipin antibody titer was found with high frequency (P<0.05); particularly significant was the high frequency with which IgMisotype was found (P<0.0l). There was no significant difference in IgG isotype titer compared to a normal healthy person. Lupus anticoagulant was not found in a

normal person but was found in 4% of Behect's syndrome patients.

2. There was no significant difference between the anticardiolipin antibody and the lupus anticoagulant in regard to sex and age.

3. In adherence to Shimizu's classification, the percentage of anticardiolipin antibody found is as fellows; 60%(9 in 15) in the complete type,47%(15 in32)in the incomplete type, 25%(3 in 12) in the suspected type, and no antibody was found in the possible type. The percentage of lupus anticoagulants found is 8% in the

incomplete type,6% in the suspected type and not found in other types.

In adherence to Lehner's classification, the percentage of anticardiolipin antibody found is as follows; 100%(1 in 1) in the neurological type, 86%(25in 29) in the mucocutaneous type,75%(20 in 26) in the arthritic type, and in the case of lupus anticoagulants, 3-8% is found in all types except the neurological type.

5. The number of clinical symptoms found at the time of the test was more than 2 in the case of anticardiolipin antibody positive and more than 3 in the case of lupus anticoagulant positive. However, there was no significant statistical

difference between the level of anticardiolipin antibody and lupus anticoagulant and the activity of disease.

6. In a1l of the cases, when a lupus anticoagulant was found, anlicardiolipin antibody was also found, and the isotype was always IgM. When a lupus anticoagulant was not found, anticardiolipin antibody was found in 86% of the cases.

7. Intravascular thrombosis was found in 23% of the patients with positive anticardiolipin antibody and the isotype was always IgM. In the case of a lupus anticoagulant positive patients intravascular thrombosis was not found.