Abnormalities of Circulating Lymphocyte Subsets in Haemophiliacs in an Aids-Free Population

Carr, R; Edmond, Elizabeth; Prescott, R. J.; Veitch, S.E.; Peutherer, J F; Steel, C. M.; Ludlam, Christopher A.

doi:10.1016/s0140-6736(84)91931-7

Cited by 89 publications

(22 citation statements)

References 25 publications

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“…They were reconstituted as directed, dispensed, stored at -70 °C, and thawed at 37 °C immediately before filtration through a thin layer of Sephadex G-200 superfine (Pharmacia, Uppsala, Sweden). The sepa- 15] even in the absence of AIDS agent [5]. It cannot be excluded that, e.g., IgG-fibrinogen complexes can be involved in the immediate adverse effects occasionally encountered aft er infusion of factor VIII preparations.…”

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confidence: 99%

Complexes of IgG and Plasma Proteins in Factor VIII Preparations - a Possible Cause of Adverse Reactions

Wadsworth¹,

Blombäck²,

Kjellman³

et al. 1985

Vox Sanguinis

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IgG in factor VIII preparations was studied as a possible cause of adverse reactions following infusion of hemophiliacs. Thin-layer immuno-gel filtration analysis of nine products from seven firms demonstrated aggregated and monomeric IgG at highly variable amounts and proportions. These factor VIII products contained from 20 to 700 mg IgG per 1000 IU of factor VIII; IgG-fibrinogen complexes were demonstrated by doubleantibody testing. A relationship is suggested between aggregated IgG and/or IgG complexes in factor VIII concentrates and adverse clinical reactions. They may also partially explain abnormalities and aberrations of the immune system previously reported in hemophiliacs.

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confidence: 99%

Complexes of IgG and Plasma Proteins in Factor VIII Preparations - a Possible Cause of Adverse Reactions

Wadsworth¹,

Blombäck²,

Kjellman³

et al. 1985

Vox Sanguinis

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“…It has been suggested that abnormalities of circulating lymphocyte subsets in hae mophiliacs may result from transfusion of foreign proteins rather than specific infection. However, the degree of ab normality does not seem to be correlated with antigen load [5] although it may improve on administration of highly purified FVIII [6], Thus it appears that the cause of such impaired cell-mediated immunity could be one or more components of intermediate-purity FVIII concentrates, present in variable amounts in these products and absent from the high-purity material. This study has shown that HMW aggregates as such do not clearly fulfil these condi tions, though it remains to be established whether their composition is crucial.…”

Section: Discussionmentioning

confidence: 99%

“…The proportion of high-molecular-weight (HMW) aggregates in one product increased on freeze-drying and heating, with fibrinogen and fibronectin being the main protein components of the HMW peak. In all other concentrates, the HMW peak was less than or equal to 5% of the total protein content and there were no differences in HMW content according to purity or method of viral inactivation.itors in patients exposed to heat-treated products [2], though heat treatment does result in the loss of FVIII clotting activity and may accentuate dénaturation of the FVIII molecule [3], However, it is now recognised that haemophiliacs treated with FVIII concentrates do develop impaired cell-mediated immunity with decreased T4/T8 ra tios [4,5] and it has been suggested that their immunolog ical status may improve on administration of highly purified FVIII [6]. Although such changes could be responses to reduction of viral load, recent work by Eibl et al [7] has demonstrated that high-molecular-weight (HMW) compo nents of FVIII preparations do decrease monocyte effector functions in vitro.…”

mentioning

confidence: 99%

High Molecular Weight Aggregate Content of Heated and Unheated Factor VIII Products Determined by Fast-Protein Liquid Chromatography

Dawes¹,

Freeman²,

Dawson³

et al. 1990

Vox Sanguinis

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The molecular-weight distribution of proteins in factor VIII concentrates has been analysed by fast-protein liquid chromatography. The proportion of high-molecular-weight (HMW) aggregates in one product increased on freeze-drying and heating, with fibrinogen and fibronectin being the main protein components of the HMW peak. In all other concentrates, the HMW peak was less than or equal to 5% of the total protein content and there were no differences in HMW content according to purity or method of viral inactivation.

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“…After the introduction of the HIV-AIDS hypothesis in 1984, Ludlam et aL studied immunodeficiency in HIV-positive and HIV-negative hemophiliacs and proposed 'that the abnormalities [low T4 to T8 cell ratios] result from transfusion of foreign proteins' (Carr et al, 1984). Likewise, Tsoukas et al concluded 'These data suggest that another factor, or factors, instead of, or in addition to, exposure to HTLV-III [old term for HIV] is required for the development of immunedysfunction in hemophiliacs' (Tsoukos et al, 1984).…”

Section: The Foreign-protein-hemophilia-aids Hypothesismentioning

confidence: 99%

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

Duesberg

1995

Genetica

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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.

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Abnormalities of Circulating Lymphocyte Subsets in Haemophiliacs in an Aids-Free Population

Cited by 89 publications

References 25 publications

Complexes of IgG and Plasma Proteins in Factor VIII Preparations - a Possible Cause of Adverse Reactions

Complexes of IgG and Plasma Proteins in Factor VIII Preparations - a Possible Cause of Adverse Reactions

High Molecular Weight Aggregate Content of Heated and Unheated Factor VIII Products Determined by Fast-Protein Liquid Chromatography

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

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