B Cell Dysfunction in Haemophilia in the Absence and Presence of HIV-1 Infection

Summary

56 haemophiliacs selected on the basis of HIV-1 antibody status, liver disease grade and mean annual dose of clotting factor concentrate used were studied. Spontaneous and stimulated IgG and IgM production in vitro were measured. HIV-1 infection was associated with increased spontaneous immunoglobulin production and an impaired response to pokeweed mitogen and Staph Aureus protein A. Implying a shift in the proportions of partially and fully activated B cells.

In the absence of HIV-L infection there was a shift to a greater proportion of partially activated B cells in patients with severe liver disease. The remainder had in vitro immunoglobulin production comparable to controls. B cell abnormalities occur early in the course of HIV-1 infection. Liver disease and not clotting factor concentrate treatment cause B cell abnormalities in the absence of HIV-1 infection in haemophilia.

• References

• 1 Fauci AS. The human immunodeficiency virus: Infectivity and mechanisms of pathogenesis. Science 1988; 239: 617-622
• 2 Wardle EN. Immunoglobulins and immunological reactions in haemophilia. Lancet 1967; i: 233-234
• 3 Levine PH, McVerry BA, Attock B, Dormandy KA. Health of the intensively treated haemophiliac with special reference to abnormal liver chemistries and splenomegaly. Blood 1977; 50: 1-9
• 4 Stevens RF, Cuthbert AC, Perara PR. et al Liver disease in haemophiliacs: an overstated problem. Br J Haematol 1983; 55: 649-655
• 5 Carr R, Veitch SE, Edmond E, Peuterer JF, Prescott RJ, Steel CM, Ludlam CA. Abnormalities of circulating lymphocyte subsets in haemophiliacs in an AIDS-free population. Lancet 1984; i: 1431-1434
• 6 Hay CRM, Preston FE, Triger DR, Greaves M, Underwood J CE, Westlake L. Predictive markers of chronic liver disease in haemophilia. Blood 1987; 69: 1595-1599
• 7 Fauci AS, Whalen G, Burch C. Activation of human B lymphocytes. XV. Spontaneously occurring and mitogen-induced indirect anti-sheep red blood cell plaque-forming cells in normal human peripheral blood. J Immunol 1980; 124: 2410-2413
• 8 Fauci AS, Lane HC, Volksman DJ. Activation and regulation of human immune responses: implications in normal and disease states. Ann Intern Med 1983; 99: 61-75
• 9 Kuritani T, Cooper MD. Human B cell differentiation. ILPokeweed mitogen-responsive B cells belong to a surface immunoglobulin D-negative subpopulation. J Exp Med 1982; 155: 1561-1566
• 10 Biagotti R, Giudizi MG, Almerigogna F. et al Abnormalities of in vitro immunoglobulin production in apparently healthy haemophiliacs: relationship with alterations of T cell subsets and with HTLV-III seropositivity. Clin Exp Immunol 1986; 63: 354-358
• 11 Brevia JA, Sequi J, Zabay JM. et al Abnormal B cell function in haemophiliacs and their relationship with factor concentrate administration. Clin Exp Immunol 1985; 59: 491-498
• 12 Ragni MV, Ruben FL, Winklestein A. et al Antibody responses to immunization of patients with haemophila with and without evidence of HTLV-III infection. J Lab Clin Med 1987; 109: 545-549
• 13 Sjamsoedin-Virser E JM, Heignen CJ, Zegers B JM, Stoop JW. Defect in B cell function in HTLV-III/LAV positive haemophilia patients. Blood 1987; 69: 1388-1393
• 14 Kelly BS, Levy JG, Sikova L. The use of the enzyme linked immunoassay (ELISA) for the detection and quantification of specific antibody from cell cultures. Immunology 1979; 37: 35-42
• 15 Kronvall G, Frommel D. Definition of staphylococcal protein A reactivity for human immunoglobulin G fragment. Immunochemistry 1970; 7: 124-127
• 16 Armitage P, Berry G. Statistical Methods in Medical Research. 2nd edn Blackwell Scientific Publications; 1985
• 17 Melby M, Froebel K, Madhok R. et al HTLV III seropositivity in European haemophiliacs exposed factor VIII concentrate imported from the USA. Lancet 1985; ii: 1444-1446
• 18 Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci AS. Abnormalities of B cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome. N Engl J Med 1983; 309: 453-458
• 19 Yarchoan R, Redfield RR, Broder S. Mechanisms of B cell activation in patients with acquired immunodeficiency syndrome and related disorders. J Clin Invest 1986; 78: 439-447
• 20 Schnittman SM, Lane CH, Higgins SE. et al Direct polyclonal activation of human B lymphocytes by the Acquired Immune Deficiency virus. Science 1986; 233: 1084-1086
• 21 Lopez C, Pellet P, Stewart J. et al Characteristics of human herpes virus 6. J Infect Dis 1988; 157: 1271-1273
• 22 Sallahuddin SZ, Ablashi DV, Markham PB. et al Isolation of a new virus HBLV, in patients with lymphoproliferative disorders. Science 1986; 234: 596-601
• 23 Madhok R, Gracie JA, Smith J, Lowe G DO, Forbes CD. Capacity to produce interleukin 2 is impaired in haemophilia in the absence and presence of HIV-1 infection. Br J Haemtol (in press);
• 24 Thorpe R, Dilger P, Dawson NJ, Barrowcliffe TW. Inhibition of interleukin 2 secretion by factor VII concentrates; A possible cause of immunosuppression in haemophiliacs. Br J Haematol 1989; 71: 387-391
• 25 Forwell M, Gray KG, MacSween RN. et al Immunosuppression following alloantigen exposure: A role for Fc-Y receptor antibodies. J Clin Lab Immunol 1986; 19: 53-57
• 26 Reienherz EL, Schlossman SF. The differentiation and function of human T lymphocytes. Cell 1980; 19: 821-827