Surface Marker Data and Functional Analysis of Hemophilia Patients with and without Antibodies to LAV1

  • E. M. Schneider
  • P. Wernet
  • P. Ostendorf
  • F. Barre-Sinoussi
  • J. C. Chermann
  • M. Kessler
  • H. Brackmann
  • H. Egli
Conference paper

Abstract

Patients with hemophilia have been reported to suffer from a series of immune dysfunctions in cellular and humoral immunity. In addition to “antigen overload” induced phenomena resulting from factor VIII and factor IX substitution, possibly via alloantigen “contamination” in the preparations, latent viral infections such as CMV, hepatitis B and non A/non B have been proposed as the responsible parameters (cf. [1] for review). The discovery of antibodies to LAV1/HTLV III in a group of these patients has sparked the discussion as to whether this type of virus contributes significantly to the pathogenesis of the immune system [2]. In contrast to the increasing percentage of hemophilia patients who have developed AIDS or AIDS-related symptoms from 1981/1982 to October 1984 [3], most recent studies indicate that the number of the cases of AIDS reported in hemophiliacs are not increasing as rapidly as those for other risk groups such as homosexuals, i. v. drug abusers, and their heterosexual partners [4–6]. Since the viral propagation in vivo is definitely related to the number of activated OKT4 positive T-cells [7], patients suffering from other multiple infections of viral, bacterial, or fungal origin are at highest risk to develop LAV1-induced immunodeficiency. This seems to be generally applicable to hemophiliacs as well. Furthermore, generalized lymphadenopathy has been reported in a number of hemophiliacs, however without direct evidence for LAV1 harboring in lymph node cells [8,9].

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References

  1. 1.
    Ragni MV, Lewis JH, Spero JA, Bontempo FA, Rabin BS (1984) Decreased helper/suppressor cell ratios after treatment with factor VIII and IX concentrates and fresh frozen plasma. AM J Med 76:206PubMedCrossRefGoogle Scholar
  2. 2.
    Goldsmith JC, Moseley PL, Monick M, Brady M, Hunninghake GW (1983) T-lymphocyte subpopulation abnormalities in apparently healthy patients with hemophilia. Ann In Med 98:294Google Scholar
  3. 3.
    Gürtler LG, Wernicke D, Eberle J, Zoulek G, Deinhardt F, Schramm W (1984) Increase in prevalance of anti-HTLV III in haemophiliacs. Lancet December 1:1275CrossRefGoogle Scholar
  4. 4.
    Kitchen LW, Barin F, Sullivan JL et al. (1984) Aetiology of AIDS: Antibodies to human T-cell leukaemia virus (type III) in haemophiliacs. Nature 312:367PubMedCrossRefGoogle Scholar
  5. 5.
    Evatt BL, Gomperts ED, McDougal JS et al. (1985) Coincidental appearance of LAV I/HTLV III antibodies in hemophiliacs and the onset of the AIDS epidemic. N Engl J Med 312:483PubMedCrossRefGoogle Scholar
  6. 6.
    Eyster ME, Goedert JJ, Sarngadharan MG, Weiss SH, Gallo RC, Blattner WA (1985) Development and early natural history of HTLV III antibodies in persons with hemophilia. JAMA 253:2219PubMedCrossRefGoogle Scholar
  7. 7.
    Montagnier L et al. (1984) A new human T-lymphotropic retrovirus: characterization and possible role in lymphadenopathy and acquired immune deficiency syndromes. In: Human T-cell leukemia lymphoma viruses. (Ed: Gallo RC, Essex M, Gross L.) Cold Spring Harbour, New York, p 363Google Scholar
  8. 8.
    Andes WA, deShazo RD, Reed RJ, Harkin JC, Wang NNS (1984) Studies of lymph nodes from patients with classical hemophilia. Blood 64:768PubMedGoogle Scholar
  9. 9.
    Ragni MV, Winkelstein A, Evans TL, Lewis JH, Bontempo FA, Spero JA, Rabin BS (1984) T-lymphocyte colony assay in hemophiliacs. Blood 64:105PubMedGoogle Scholar
  10. 10.
    Wernet P, Muller CP, Ostendorf P (1984) Reactivity of lymphocytic and myelocytic leukemia blasts with monoclonal antibodies specific for the different human class II molecules. Disease Markers 2:449Google Scholar
  11. 11.
    Schneider EM, Pawelec GP, Shi LR, Uchanska-Ziegler B, Burning HJ, Wernet P (1984) TÜ69, a new monoclonal antibody to the human interleukin 2 receptor. I. Specificity and inhibitory activity for T-cell function, submittedGoogle Scholar
  12. 12.
    Pawelec GP, Hadam MR, Ziegler A et al. (1982) Long term culture, cloning, and surface markers of mixed lymphocyte-derived human T-lymphocytes with natural killer-like cytotoxicity. J Immunol 128:1892PubMedGoogle Scholar
  13. 13.
    Popovic M, Sarngadharan MG, Reed E et al. (1984) Detection, isolation, and continuous production of cytopathic human T-lymphotropic retrovirus (HTLV III) from patients with AIDS and pre-AIDS. Science 224:497PubMedCrossRefGoogle Scholar
  14. 14.
    Sarin PS, Aoki T, Shibata A et al. (1983) High incidence of human type-C retrovirus (HTLV) in family members of a HTLV-positive Japanese T-cell leukemia patient. Proc Natl Acad Sci 80:2370PubMedCrossRefGoogle Scholar
  15. 15.
    Gill JC, Menitove JE, Dana W, Wheeler D, Aster RH, Montgomery RR (1983) Generalized lymphadenopathy and T-cell abnormalities in hemophilia A. J Pediatr 103:18PubMedCrossRefGoogle Scholar
  16. 16.
    Nicholson JKA, McDougal JS, Spira TJ, Cross GD, Jones BM, Reinherz EL (1983) Immuno-regulatory subsets of the T-helper and T-suppressor cell population in homosexual men with chronic unexplained lymphadenopathy. J Clin Invest 73:191CrossRefGoogle Scholar
  17. 17.
    Miyakoshi H, Koide H, Aoki T (1984) In vitro antibody-dependent cellular cytotoxicity against human T-cell leukemia/lymphoma virus (HTLV)-producing cells. Int J Cancer 33:287PubMedCrossRefGoogle Scholar
  18. 18.
    Gatenbfy PA, Kansas GS, Xian CY, Evans RL, Engleman EG (1982) Dissection of immuno-regulatory subpopulations of T-lymphocytes within the helper and suppressor sublineages in man. J Immunol 129:1997Google Scholar
  19. 19.
    Sasportes M, Wollmann E, Cohen D, Carosella E, Bensussan A, Fradelizi D, Dausset J (1980) Suppression of the human allogeneic response in vitro with primed lymphocyte and suppressive supernatants. J Exp Med 152:270Google Scholar
  20. 20.
    Armstrong JA, Dawkins RL, Horne R (1985) Retroviral infection of accessory cells and the immunological paradox in AIDS. Immunology Today 6:121CrossRefGoogle Scholar
  21. 21.
    Klatzmann D, Champagne E, Chamaret S, Gruest J, Guetard D, Hercend T, Gluckman J-C, Montagnier L (1984) T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 312:767PubMedCrossRefGoogle Scholar
  22. 22.
    Dalgleish AG, Beverly PCL, Clapham PR, Crawford DH, Greaves MF, Weiss RA (1984) The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312:763PubMedCrossRefGoogle Scholar
  23. 23.
    Hasset JM, Zaroulis CG, Greenberg ML, Siegal FP (1983) Bone marrow transplantation in AIDS. N Engl J Med 309:665Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • E. M. Schneider
    • 1
    • 2
    • 3
  • P. Wernet
    • 1
    • 2
    • 3
  • P. Ostendorf
    • 1
    • 2
    • 3
  • F. Barre-Sinoussi
    • 1
    • 2
    • 3
  • J. C. Chermann
    • 1
    • 2
    • 3
  • M. Kessler
    • 1
    • 2
    • 3
  • H. Brackmann
    • 1
    • 2
    • 3
  • H. Egli
    • 1
    • 2
    • 3
  1. 1.TübingenGermany
  2. 2.BonnGermany
  3. 3.ParisFrance

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