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有和没有感染HIV的血友病患者中由外源蛋白介导的免疫缺陷

Foreign-protein-mediated immunodeficiency in hemophiliacs with and without HIV.

作者信息

Duesberg P H

机构信息

Dept. of Molecular and Cell Biology, University of California at Berkeley 94720, USA.

出版信息

Genetica. 1995;95(1-3):51-70. doi: 10.1007/BF01435001.

Abstract

Hemophilia-AIDS has been interpreted in terms of two hypotheses: the foreign-protein-AIDS hypothesis and the Human Immunodeficiency Virus (HIV)-AIDS hypothesis. The foreign-protein-AIDS hypothesis holds that proteins contaminating commercial clotting factor VIII cause immunosuppression. The foreign-protein hypothesis, but not the HIV hypothesis, correctly predicts seven characteristics of hemophilia-AIDS: 1) The increased life span of American hemophiliacs in the two decades before 1987, although 75% became infected by HIV--because factor VIII treatment, begun in the 1960s, extended their lives and simultaneously disseminated harmless HIV. After 1987 the life span of hemophiliacs appears to have decreased again, probably because of widespread treatment with the cytotoxic anti-HIV drug AZT. 2) The distinctly low, 1.3-2%, annual AIDS risk of hemophiliacs, compared to the higher 5-6% annual risk of intravenous drug users and male homosexual aphrodisiac drug users--because transfusion of foreign proteins is less immunosuppressive than recreational drug use. 3) The age bias of hemophilia-AIDS, i.e. that the annual AIDS risk increased 2-fold for each 10-year increase in age--because immunosuppression is a function of the lifetime dose of foreign proteins received from transfusions. 4) The restriction of hemophilia-AIDS to immunodeficiency diseases--because foreign proteins cannot cause non-immunodeficiency AIDS diseases, like Kaposi's sarcoma. 5) The absence of AIDS diseases above their normal background in sexual partners of hemophiliacs--because transfusion-mediated immunotoxicity is not contagious. 6) The occurrence of immunodeficiency in HIV-free hemophiliacs--because foreign proteins, not HIV, suppress their immune system. 7) Stabilization, even regeneration, of immunity of HIV-positive hemophiliacs by long-term treatment with pure factor VIII. This shows that neither HIV nor factor VIII plus HIV are immunosuppressive by themselves. Therefore, AIDS cannot be prevented by elimination of HIV from the blood supply and cannot be rationally treated with genotoxic antiviral drugs, like AZT. Instead, hemophilia-AIDS can be prevented and has even been reverted by treatment with pure factor VIII.

摘要

血友病 - 艾滋病已根据两种假说来解释:外来蛋白质 - 艾滋病假说和人类免疫缺陷病毒(HIV) - 艾滋病假说。外来蛋白质 - 艾滋病假说认为,污染商业凝血因子VIII的蛋白质会导致免疫抑制。外来蛋白质假说而非HIV假说正确地预测了血友病 - 艾滋病的七个特征:1)1987年之前的二十年里美国血友病患者寿命延长,尽管75%的患者感染了HIV——因为始于20世纪60年代的因子VIII治疗延长了他们的生命,同时传播了无害的HIV。1987年之后血友病患者的寿命似乎又下降了,可能是因为广泛使用了细胞毒性抗HIV药物AZT进行治疗。2)血友病患者明显较低的每年1.3% - 2%的艾滋病风险,相比之下静脉吸毒者和男性同性恋壮阳药使用者每年5% - 6%的较高风险——因为输入外来蛋白质的免疫抑制作用比使用消遣性药物要小。3)血友病 - 艾滋病的年龄偏差,即每增加10岁,每年的艾滋病风险增加2倍——因为免疫抑制是从输血中接受的外来蛋白质终身剂量的函数。4)血友病 - 艾滋病仅限于免疫缺陷疾病——因为外来蛋白质不会导致非免疫缺陷性艾滋病疾病,如卡波西肉瘤。5)血友病患者的性伴侣中艾滋病疾病没有超过其正常背景水平——因为输血介导的免疫毒性不具有传染性。6)未感染HIV的血友病患者出现免疫缺陷——因为是外来蛋白质而非HIV抑制了他们的免疫系统。7)通过长期使用纯因子VIII治疗,HIV阳性血友病患者的免疫力得以稳定,甚至恢复。这表明HIV本身以及因子VIII加HIV都不会产生免疫抑制作用。因此,通过从血液供应中消除HIV无法预防艾滋病,也不能用具有基因毒性的抗病毒药物如AZT进行合理治疗。相反,血友病 - 艾滋病可以通过使用纯因子VIII进行预防,甚至已经得到逆转。

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