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DOI: 10.1055/s-0038-1651602
The Course of Preexistent Immune Abnormalities in HIV Negative Haemophiliacs Treated for Two Years with a Monoclonal Purified Factor VIII Concentrate
Publication History
Received 05 June 1992
Accepted after revision 01 December 1992
Publication Date:
05 July 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199304/lookinside/thumbnails/10-1055-s-0038-1651602-1.jpg)
Summary
The administration of factor VIII concentrates has been associated with immune abnormalities in patients with severe haemophilia A, even in the absence of HIV infection.
The effects of a monoclonal purified factor VIII concentrate, Hemofil M (Baxter), on preexistent immune abnormalities were assessed over a 2 year period in 22 HIV negative haemophiliacs. They were treated previously with other concentrates, and received Hemofil T from 1983 to 1988. No HIV infection was demonstrated. No serologic evidence for other viral (re)-infections was seen. A decrease of HLA-DR expression on non-B lymphocytes in the first year (P = 0.026), and a decrease of T4-T8 ratio over the 2 years were found (P = 0.0016). Skin tests were non-contributive. The decrease in HLA-DR expression is suggestive for an improved immune function, possibly due to a reduced content of protein or virus in this concentrate.
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References
- 1 Anonymous. Blood transfusions, haemophilia, and AIDS. Lancet 1984; ii: 1433-1435
- 2 Goedert JJ, Sarngadharan MG, Eyster ME, Weiss SH, Bodner AJ, Gallo RC, Blattner WA. Antibodies reactive with human T cell leucaemia viruses in the serum of hemophiliacs receiving factor VIII concentrate. Blood 1985; 65: 492-495
- 3 Ragni MV, Winkelstein A, Kingsley L, Spero JA, Lewis JH. 1986 update of HIV seroprevalence, seroconversion, AIDS incidence, and immunologic correlates of HIV infection in patients with hemophilia A and B. Blood 1987; 70: 786-790
- 4 Noel L, Guerois C, Maisonneuve P, Verroust F, Laurian Y. Antibodies to hepatitis C virus in haemophilia. Lancet 1989; ii: 560 (Letter)
- 5 Jones PK, Ratnoff OD. The changing prognosis of classic hemophilia (factor VIII “deficiency”). Ann Intern Med 1991; 114: 641-684
- 6 McDougal JS, Martin LS, Cort SP, Mozen M, Heldebrant CM, Evatt BL. Thermal inactivation of the acquired immunodeficiency syndrome virus, human T lymphotropic virus-III/lymphadenopathy-associated virus, with special reference to antihemophiliac factor. J Clin Invest 1985; 76: 875-877
- 7 Rouzzioux C, Chamaret S, Montagnier L, Carnelli V, Rolland G, Mannucci PM. Absence of antibodies to aids virus in heamophiliacs treated with heat-treated factor VIII concentrate. Lancet 1985; i: 271-2 (Letter)
- 8 Meer Jvd, Daenen S, Imhoff GWv, Wolf JTMde, Halie MR. Absence of seroconversion for HTLV-III in haemophiliacs intensively treated with factor VIII concentrate. Br Med J 1986; 292: 1049
- 9 Mannucci PM, Colombo M. Virucidal treatment of clotting factor concentrates. Lancet 1988; ii: 782-786
- 10 Busch MP, Eble BE, Khayam-Bashi H, Heilbron D, Murphy EL, Kwok S, Sninsky J, Perkins HA, Vyas GN. Evaluation fo screened blood donations for human immunodeficiency virus type 1 infection by culture and DNA amplification of pooled cells. N Engl J Med 1991; 325: 1-5
- 11 Kreis JK, Kitchen LW, Prince HE, Kasper CK, Goldstein AL, Naylor PH, Preble O, Stewart JA, Essex M. Human T cell leukemia virus type III antibody, lymphadenopathy, and acquired immune deficiency syndrome in hemophiliac subjects. Am J Med 1986; 80: 345-350
- 12 Knutsen AP, Bouhasin JD, Joist JH, Scrivner D, Mueller KR, Gioia K, Janney S. Decrease of CD4 cell number and function in HIV-seropositive hemophiliacs in a longitudinal study. Ann Allergy 1989; 63: 189-194
- 13 Weintrub PS, Koerper MA, Addiego JE, Drew L, Lennette ET, Miner R, Cowan MJ, Ammann AJ. Immunologic abnormalities in patients with hemophilia A. J Pediatr 1983; 103: 692-695
- 14 Kimberley RP, Inman RD, Bussel JB, Polk JR, Hilgartner M. Modulation of mononuclear phagocyte system function and circulating immunecomplexes by lyophilized concentrates in patients with classic hemophilia. Clin Immunol Immunopathol 1984; 31: 321-330
- 15 Mannhalter JW, Zlabinger GJ, Ahmad R, Zielinski CC, Schramm W, Eibl MM. A functional defect in the early phase of the immune response observed in patients with hemophilia A. Clin Immunol Immunopathol 1986; 38: 390-397
- 16 Mannhalter JW, Ahmad R, Leibl H, Gottlicher J, Wolf HM, Eibl MM. Comparable modulation of human monocyte functions by commercial factor VIII concentrates of varying purity. Blood 1988; 71: 1662-1668
- 17 Pasi KJ, Hill FGH. In vitro and in vivo inhibition of monocyte phygocytic function by factor VIII concentrates: correlation with concentrate purity. Br J Haematol 1990; 76: 88-93
- 18 Lederman MM, Ratnoff OD, Shoger T. Antihemophilic factor preparations inhibit lymphocyte function & alter lymphocyte subsets in culture. Clin Research. 1984 32. suppl 313 (abstr)
- 19 Lederman MM, Saunders C, Toossi Z, Lemon N, Everson B, Ratnoff OD. Antihemophilic factor (factor VIII) preparations inhibit lymphocyte proliferation and production of interleukin-2. J Lab Clin Med 1986; 107: 471-478
- 20 Madhok R, Gracie A, Lowe GDO, Burnett A, Froebel K, Follett E, Forbes CD. Impaired cell mediated immunity in haemophilia in the absence of infection with human immunodeficiency virus. Br Med J 1986; 293: 978-980
- 21 Mahir WS, Millard RE, Booth JC, Flute PT. Functional studies of cell-mediated immunity in haemophilia and other bleeding disorders. Br J Haematol 1988; 69: 367-370
- 22 Thorpe R, Dilger P, Dawson NJ, Barrowcliffe TW. Inhibition of interleukin-2 secretion by factor VIII concentrates: a possible cause of immunosuppression in haemophiliacs. Br J Haematol 1989; 71: 387-391
- 23 Hay CRM, McEvoy P, Duggan-Keen M. Inhibition of lymphocyte IL2-receptor expression by factor VIII concentrate: a possible cause of immunosuppression in haemophiliacs. Br J Haematol 1990; 75: 278-281
- 24 Madhok R, Gracie JA, Smith J, Lowe GDO, Forbes CD. Capacity to produce interleukin 2 is impaired in haemophilia in the absence and presence of HIV 1 infection. Br J Haematol 1990; 76: 70-74
- 25 Madhok R, Smith J, Jenkins A, Lowe GDO. T cell sensitization to factor VIII in haemophilia A?. Br J Haematol 1991; 79: 235-238
- 26 Gomez E, Alberca I, Gonzalez M, Zaballoz R, Vicente V. Effect of hepatitis C virus infection on the lymphoid population in hemophiliacs. Blood 1991; 77: 1399-1400
- 27 Weinstein RE. Immunoaffinity purification of factor VIII. Ann Clin Lab Science 1989; 19: 84-91
- 28 Seremetis S, Aledort LM. Sacks H and the monoclate study group Differential effects on CD4 cell counts of high or intermediate grade purity factor VIII concentrates in HIV + haemophiliacs: a metaanalysis. Blood 1990; 76 1624: 408a
- 29 Mansour I, Doinel C, Rouger P. Dichotomy of two CD8 + lymphocyte subsets in HIV infection. Depletion of CD8 + CD3- and expansion of CD8 + CD3 + subsets: consequence on the CD4/CD8 ratio. Clin Exp Immunol 1991; 85: 481-484
- 30 Prince HE, Kreiss JK, Kasper CK, Kleinman S, Saunders AM, Waldbeser L, Mandigo G, Kaplan HS. Distinctive lymphocyte subpopulation abnormalities in patients with congenital coagulation disorders who exhibit lymph node enlargement. Blood 1985; 66: 64-68
- 31 Shannon BT, Roach J, Cheek-Luten M, Orosz C, Ruymann FB. Progressive change in lymphocyte distribution and degree of hyper-gammaglobulinemia with age in children with hemophilia. J Clin Immunol 1986; 6: 121-129
- 32 Sullivan JL, Brewster FE, Brettler DB, Forsberg AD, Cheeseman SH, Byron KS, Baker SM, Willitts DL, Lew RA, Levine PH. Hemophiliac immunodeficiency: influence of exposure to factor VIII concentrate, LAV/HTLV-III, and herpesviruses. J Pediatrics 1986; 108: 504-510
- 33 Dianzani U, Pileri A, Bianchi A, Camponi A, Tamponi G, Massaia M. Biochemical and immunologic abnormalities in peripheral blood T lymphocytes of patients with hemophilia A. Eur J Haematol 1988; 41: 334-340
- 34 Cuthbert RJG, Ludlam CA, Steel CM, Beatson D, Peutherer JF. Immunological studies in HIV seronegative haemophiliacs: relationships to blood product therapy. Br J Haematol 1992; 80: 364-369
- 35 Cotner T, Williams JM, Cristenson L, Shapiro HM, Strom TB, Strominger J. Simultaneous flow cytometric analysis of human T-cell activation antigen expression and DNA content. J Exp Med 1983; 157: 461-472
- 36 Nouri-Aria KT, Magrin S, Alexander GJM, Anderson MG, Williams R, Eddleston ALWF. Abnormal T-cell activation in chronic hepatitis B viral infection: a consequence of monocyte dysfunction?. Immunology 1988; 64: 733-738
- 37 Robbins PA, Maino VC, Warner NL, Brodsky FM. Activated T cells and monocytes have characteristic patterns of class II antigen expression. J Immunol 1988; 141: 1281-1287
- 38 Schramm W, Roggendorf M, Rommel F, Kammerer R, Pohlmann H, Rashofer R, Gurtler L, Deinhardt F. Prevalence of antibodies to hepatitis C virus (HCV) in haemophiliacs. Blut 1989; 59: 390-392
- 39 Brettler DB, Alter HJ, Dienstag JL, Forsberg AD, Levine PH. Prevalence of hepatitis C virus antibody in a cohort of haemophilia patients. Blood 1990; 76: 254-256
- 40 Brettler DB, Forsberg AD, Levine PH, Petillo J, Lamon K, Sullivan JL. Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies. Blood 1989; 73: 1859-1863
- 41 Roosendaal FR, Varekamp I, Smit C, Bröcker-Vriends AHJT, Dijck Hv, Van den Broucke JP, Hermans J, Suurmeijer TPBM, Briët E. Mortality and causes of death in Dutch haemophiliacs 1973-86. Br J Haematol 1989; 71: 71-76
- 42 Hay C. Purity aspects of ultra-pure concentrates: is pure better?. R Soc Med Serv, Round Table Ser 1991; 25: 69-77