3.抗リン脂質抗体
「はじめに」 抗リン脂質抗体(aPLA)は血栓症との関連が注目され, 検査項目としてはループスアンチコアグラント(LA), 抗カルジオリピン抗体(aCL), β2-glycoprotein I(β2-GPI)依存性抗カルジオリピン抗体などが知られている. 本シンポジウムではaPLAが脳梗塞の独立した危険因子となるかどうか, 次に各種aPLAと脳梗塞の再発, 予後との関係について検討し, さらに血栓発症の機序を解明する目的で, 抗カルジオリピン抗体がprotein C活性化に障害を及ぼすか否かについて検討した. 「1. 抗リン脂質抗体の測定」 抗リン脂質抗体のうち, 臨床的に重要とされているのは...
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Published in | 脳卒中 Vol. 21; no. 4; pp. 446 - 451 |
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Main Author | |
Format | Journal Article |
Language | Japanese |
Published |
一般社団法人 日本脳卒中学会
25.12.1999
日本脳卒中学会 |
Online Access | Get full text |
ISSN | 0912-0726 1883-1923 |
DOI | 10.3995/jstroke.21.4_446 |
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Abstract | 「はじめに」 抗リン脂質抗体(aPLA)は血栓症との関連が注目され, 検査項目としてはループスアンチコアグラント(LA), 抗カルジオリピン抗体(aCL), β2-glycoprotein I(β2-GPI)依存性抗カルジオリピン抗体などが知られている. 本シンポジウムではaPLAが脳梗塞の独立した危険因子となるかどうか, 次に各種aPLAと脳梗塞の再発, 予後との関係について検討し, さらに血栓発症の機序を解明する目的で, 抗カルジオリピン抗体がprotein C活性化に障害を及ぼすか否かについて検討した. 「1. 抗リン脂質抗体の測定」 抗リン脂質抗体のうち, 臨床的に重要とされているのはlupus anticoagulant(LA)1)と抗カルジオリピン抗体(aCL)2)-4)である. LAの存在はスクリーニングテストとしてA-PTTを測定し, APTTが延長している場合, 患者血漿と正常血漿を等量混合する血漿混合試験(cross mixing study)を行い, A-PTTの延長が正常化されない場合には, リン脂質依存性であることを確認してLA陽性とした. aCLはELISA法を, β2-GPI依存性aCLはYAMASA kitを用いて測定した. 「2. 抗リン脂質抗体は脳梗塞の危険因子となるか」 対象はSLEを基礎疾患としない脳梗塞273例とSLEを基礎疾患とする脳梗塞12例, 合計285例で, それぞれの群での抗リン脂質抗体の陽性率および脳血管障害の危険因子の出現率を検討した. その結果, SLEを基礎疾患としない脳梗塞273例のうちaPLA陽性例は24例, 8.8%, SLEを基礎疾患とする脳梗塞12例中aPLA陽性例は8例, 67%であった. SLEを基礎疾患としないaPLA陽性脳梗塞24例のうち高血圧, 糖尿病などの危険因子のない例は38%で, aPLA陰性例での15%に比べ有意に高く, aPLAは脳梗塞の独立した危険因子と考えられた(表1). 米国抗リン脂質抗体共同研究グループであるAPASS 5)はaCL陽性者は陰性者に比べて2.31倍の危険率で脳梗塞をおこしやすく, 本抗体は脳梗塞の独立したリスクファクターであると報告している. |
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AbstractList | 「はじめに」 抗リン脂質抗体(aPLA)は血栓症との関連が注目され, 検査項目としてはループスアンチコアグラント(LA), 抗カルジオリピン抗体(aCL), β2-glycoprotein I(β2-GPI)依存性抗カルジオリピン抗体などが知られている. 本シンポジウムではaPLAが脳梗塞の独立した危険因子となるかどうか, 次に各種aPLAと脳梗塞の再発, 予後との関係について検討し, さらに血栓発症の機序を解明する目的で, 抗カルジオリピン抗体がprotein C活性化に障害を及ぼすか否かについて検討した. 「1. 抗リン脂質抗体の測定」 抗リン脂質抗体のうち, 臨床的に重要とされているのはlupus anticoagulant(LA)1)と抗カルジオリピン抗体(aCL)2)-4)である. LAの存在はスクリーニングテストとしてA-PTTを測定し, APTTが延長している場合, 患者血漿と正常血漿を等量混合する血漿混合試験(cross mixing study)を行い, A-PTTの延長が正常化されない場合には, リン脂質依存性であることを確認してLA陽性とした. aCLはELISA法を, β2-GPI依存性aCLはYAMASA kitを用いて測定した. 「2. 抗リン脂質抗体は脳梗塞の危険因子となるか」 対象はSLEを基礎疾患としない脳梗塞273例とSLEを基礎疾患とする脳梗塞12例, 合計285例で, それぞれの群での抗リン脂質抗体の陽性率および脳血管障害の危険因子の出現率を検討した. その結果, SLEを基礎疾患としない脳梗塞273例のうちaPLA陽性例は24例, 8.8%, SLEを基礎疾患とする脳梗塞12例中aPLA陽性例は8例, 67%であった. SLEを基礎疾患としないaPLA陽性脳梗塞24例のうち高血圧, 糖尿病などの危険因子のない例は38%で, aPLA陰性例での15%に比べ有意に高く, aPLAは脳梗塞の独立した危険因子と考えられた(表1). 米国抗リン脂質抗体共同研究グループであるAPASS 5)はaCL陽性者は陰性者に比べて2.31倍の危険率で脳梗塞をおこしやすく, 本抗体は脳梗塞の独立したリスクファクターであると報告している. |
Author | 北川, 泰久 |
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References | 22) Shi W, Chong H, Hoggs PJ, et al : Anticardiolipin antibodies block the inhibition by β2-glycoprotein I of the factor Xa generating activity of platelets. Thromb Haemost 70:342-345, 1993 26) Tuhrim S, Rand JH, Wu X, et al : Antiphosphatidyl serone antibodies are independently associated with ischemic stroke. Neurology 53:1523-1527, 1999 11) Levine SR, Salowich-Palm L, Sawaya KL, et al : IgG anticardiolipin antibody titer>40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study. Stroke 28:1660-1665, 1997 15) Brey RL : Stroke prevention in patients with an-tiphospholipid antibodies. Lupus 3:299-302, 1994 24) Toschi V, Motta A, Castelli C, et al : Prevalence and clinical significance of antiphospholipid antibodies to noncardiolipin antigens in systemic lupus erythematosus. Haemostasis 23:275-283, 1993 17) The Warfarin-Aspirin Recurrent Stroke Study (WARSS), The Antiphospholipid Antibodies and Stroke Study (APASS), The Patent Foramen Ovale in Cryptogenic Stroke Study (PICSS), The Hemostatic System Activation Study (HAS), The Genes in Stroke (GENESIS) Study. The feasibility of a collaborative double-blind study using an anticoagulant. Cerebrovasc Dis 7:100-112, 1997 7) The Antiphospholipid Antibodies in Stroke Study Group : Clinical and laboratory findings in patients with antiphospholipid antibodies and cerebral ischemia. Stroke 21:1268-1273, 1990 20) Cariou R, Tobelem G, Soria C, et al : Inhibition of protein C activation by endothelial cells in the presence of lupus anticoagulant. N Eng J Med 314:1193-1194, 1986 3) Galli M, Comfurius P, Maassen C, et al : Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 335 1544-1547,1990 4) Koike T, Matsuura E : Anti-beta 2-glycoprotein I antibody : specificity and clinical significance. Lupus 5:378-380, 1996 5) The Antiphospholipid Antibodies in Stroke Study (APASS) Group : Anticardiolipin antibodies are an independent risk factor for first ischemic stroke. Neurology 43:2069-2073. 1993 21) Ginsberg JS, Domers C, Brill-Edwards P, et al : Increased thrombin generation and activity in patients with systemic lupus erythematosus and an-ticardiolipin antibodies : evidence for a prothrombotic state. Blood 81:2558-2563, 1993 1) Brandt JT, Triplett DA, Alving B, et al : Criteria for the diagnosis of lupus anticoagulants : An update. On behalf of the subcommittee on lupus anticoagulant/antiphospholipid antibody of the scientific and standardisation committee of the ISTH. Thromb Haemost 74:1185-1190, 1995 2) Harris EN, Gharavi AE, Boey ML, et al : Anticardiolipin antibodies : detection by radioimmu-noassay and association with thrombosis in systemic lupus erythematosus. Lancet 2:1211-1214, 1983 8) Levine SR, Brey RL, Joseph CLM, et al : Risk of recurrent thromboembolic events in patients with focal cerebral ischemia and antiphospholipid antibodies. Stroke 23 [suppl 1.] : I-29-I-32, 1992 6) Levine SR, Deegan MJ, Futrell N, et al : Cere-brovascular and neurologic disease associated with antiphospholipid antibodies : 48 cases. Neurology 40:1181-1189, 1990 9) 北川泰久,篠原幸人,丹羽潔ら:本邦における抗カルジオリピン抗体陽性脳梗塞の再発および予後に関する検討.臨床神経 34:799-804, 1994 25) Toschi V, Motta A, Castelli C, et al : High prevalence of antiphosphatidylinositol antibodies in young patients with cerebral ischemia of undetermined cause. Stroke 29:1759-1764, 1998 13) Feldmann E, Levine SR : Cerebrovascular disease with antiphospholipid antibodies : Immune mechanisms, significance, and therapeutic options. Ann Neurol 37(S1) : S114-S130. 1995 18) De Groot PG, Derksen RHWM : Protein C pathway, antiphospholipid antibodies and thrombosis. Lupus 3:229-233, 1994 23) Horkko S, Miller E, Dudl E, et al : Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein. J Clin Invest 98:815-825, 1996 14) Babikian VL, Levine SR : Therapeutic considerations for stroke patients with antiphospholipid antibodies. Stroke 23 [suppl 1.] : I-33-I-37, 1992 10) Antiphospholipid Antibodies in Stroke Study (APASS) group : Anticardiolipin antibodies and the risk of recurrent thrombo-occulusive events and death. Neurology 47:91-94, 1997 16) Khamashta MA, Jose Cuadrare M, Mujie F, et al: The management of thrombosis in the antiphospholipid antibody syndrome. N Eng J Med 332:993-997, 1995 19) Comp PC, Debault LE, Ramon NL, et al : Human thrombomodulin is inhibited by IgG from two patients with nonspecific anticoagulants. Blood 62 (Suppl) : 299a, 1983 12) Triplett DA, Brandt JT, Musgrave KA, et al : The relationship between lupus anticoagulant and antibodies to phospholipids. JAMA 259:550-554, 1988 |
References_xml | – reference: 5) The Antiphospholipid Antibodies in Stroke Study (APASS) Group : Anticardiolipin antibodies are an independent risk factor for first ischemic stroke. Neurology 43:2069-2073. 1993 – reference: 22) Shi W, Chong H, Hoggs PJ, et al : Anticardiolipin antibodies block the inhibition by β2-glycoprotein I of the factor Xa generating activity of platelets. Thromb Haemost 70:342-345, 1993 – reference: 8) Levine SR, Brey RL, Joseph CLM, et al : Risk of recurrent thromboembolic events in patients with focal cerebral ischemia and antiphospholipid antibodies. Stroke 23 [suppl 1.] : I-29-I-32, 1992 – reference: 11) Levine SR, Salowich-Palm L, Sawaya KL, et al : IgG anticardiolipin antibody titer>40 GPL and the risk of subsequent thrombo-occlusive events and death. A prospective cohort study. Stroke 28:1660-1665, 1997 – reference: 12) Triplett DA, Brandt JT, Musgrave KA, et al : The relationship between lupus anticoagulant and antibodies to phospholipids. JAMA 259:550-554, 1988 – reference: 10) Antiphospholipid Antibodies in Stroke Study (APASS) group : Anticardiolipin antibodies and the risk of recurrent thrombo-occulusive events and death. Neurology 47:91-94, 1997 – reference: 1) Brandt JT, Triplett DA, Alving B, et al : Criteria for the diagnosis of lupus anticoagulants : An update. On behalf of the subcommittee on lupus anticoagulant/antiphospholipid antibody of the scientific and standardisation committee of the ISTH. Thromb Haemost 74:1185-1190, 1995 – reference: 18) De Groot PG, Derksen RHWM : Protein C pathway, antiphospholipid antibodies and thrombosis. Lupus 3:229-233, 1994 – reference: 16) Khamashta MA, Jose Cuadrare M, Mujie F, et al: The management of thrombosis in the antiphospholipid antibody syndrome. N Eng J Med 332:993-997, 1995 – reference: 23) Horkko S, Miller E, Dudl E, et al : Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein. J Clin Invest 98:815-825, 1996 – reference: 4) Koike T, Matsuura E : Anti-beta 2-glycoprotein I antibody : specificity and clinical significance. Lupus 5:378-380, 1996 – reference: 15) Brey RL : Stroke prevention in patients with an-tiphospholipid antibodies. Lupus 3:299-302, 1994 – reference: 2) Harris EN, Gharavi AE, Boey ML, et al : Anticardiolipin antibodies : detection by radioimmu-noassay and association with thrombosis in systemic lupus erythematosus. Lancet 2:1211-1214, 1983 – reference: 6) Levine SR, Deegan MJ, Futrell N, et al : Cere-brovascular and neurologic disease associated with antiphospholipid antibodies : 48 cases. Neurology 40:1181-1189, 1990 – reference: 17) The Warfarin-Aspirin Recurrent Stroke Study (WARSS), The Antiphospholipid Antibodies and Stroke Study (APASS), The Patent Foramen Ovale in Cryptogenic Stroke Study (PICSS), The Hemostatic System Activation Study (HAS), The Genes in Stroke (GENESIS) Study. The feasibility of a collaborative double-blind study using an anticoagulant. Cerebrovasc Dis 7:100-112, 1997 – reference: 3) Galli M, Comfurius P, Maassen C, et al : Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 335 1544-1547,1990 – reference: 25) Toschi V, Motta A, Castelli C, et al : High prevalence of antiphosphatidylinositol antibodies in young patients with cerebral ischemia of undetermined cause. Stroke 29:1759-1764, 1998 – reference: 21) Ginsberg JS, Domers C, Brill-Edwards P, et al : Increased thrombin generation and activity in patients with systemic lupus erythematosus and an-ticardiolipin antibodies : evidence for a prothrombotic state. Blood 81:2558-2563, 1993 – reference: 19) Comp PC, Debault LE, Ramon NL, et al : Human thrombomodulin is inhibited by IgG from two patients with nonspecific anticoagulants. Blood 62 (Suppl) : 299a, 1983 – reference: 26) Tuhrim S, Rand JH, Wu X, et al : Antiphosphatidyl serone antibodies are independently associated with ischemic stroke. Neurology 53:1523-1527, 1999 – reference: 24) Toschi V, Motta A, Castelli C, et al : Prevalence and clinical significance of antiphospholipid antibodies to noncardiolipin antigens in systemic lupus erythematosus. Haemostasis 23:275-283, 1993 – reference: 13) Feldmann E, Levine SR : Cerebrovascular disease with antiphospholipid antibodies : Immune mechanisms, significance, and therapeutic options. Ann Neurol 37(S1) : S114-S130. 1995 – reference: 14) Babikian VL, Levine SR : Therapeutic considerations for stroke patients with antiphospholipid antibodies. Stroke 23 [suppl 1.] : I-33-I-37, 1992 – reference: 20) Cariou R, Tobelem G, Soria C, et al : Inhibition of protein C activation by endothelial cells in the presence of lupus anticoagulant. N Eng J Med 314:1193-1194, 1986 – reference: 7) The Antiphospholipid Antibodies in Stroke Study Group : Clinical and laboratory findings in patients with antiphospholipid antibodies and cerebral ischemia. Stroke 21:1268-1273, 1990 – reference: 9) 北川泰久,篠原幸人,丹羽潔ら:本邦における抗カルジオリピン抗体陽性脳梗塞の再発および予後に関する検討.臨床神経 34:799-804, 1994 |
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Snippet | 「はじめに」 抗リン脂質抗体(aPLA)は血栓症との関連が注目され, 検査項目としてはループスアンチコアグラント(LA), 抗カルジオリピン抗体(aCL), β2-glycoprotein I(β2-GPI)依存性抗カルジオリピン抗体などが知られている.... |
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Title | 3.抗リン脂質抗体 |
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