Abstract
Three children, all girls, showed long-lasting clinical and serologic evidence of chronic active Epstein-Barr virus (EBV) infection. Extremely high serum titers of IgG- and IgA-type VCA antibodies and EA antibodies were present, whereas EBNA antibody titers were in the range of those found in seropositive individuals. All three patients repeatedly showed the presence of nonspecific pokeweed mitogen (PWM)-activatable suppressor cells in the peripheral blood. The analysis of EBV-specific cytotoxic T cells showed that one patient exhibited normal cytotoxicity, whereas a second patient demonstrated no EBV-specific cytotoxicity together with unusually high levels of virus-infected B cells in the blood and lymph node. The third patient repeatedly showed refractoriness of the circulating B cells to EBV infection, probably on the basis of some developmental defect. It was concluded that each patient has his or her own peculiar defect in the virus-host balance, indicating that heterogeneity may underlie the syndrome of chronic active EBV infection in humans.
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References
Andiman WA: The Epstein-Barr virus and EB virus infections in childhood. J Pediat 95:171–182, 1979
Waele M de, Tielemans CH, van Camp BKG: Characterization of immunoregulatory T cells in EBV induced mononucleosis by monoclonal antibodies. N Engl J Med 8:460–461, 1981
Mangi RJ, Niederman JC, Kelleher JE Jr,et al. Depression of cell-mediated immunity during acute infectious mononucleosis. N Engl J Med 291:1149–1153, 1974
Wallace LE, Rickinson AB, Rowe M,et al. Stimulation of human lymphocytes with irradiated cells of the autologous Epstein-Barr virus-transformed cell line. Cell Immunol 67:129–140, 1982
Haynes BF, Schooley RT, Payling-Wright ChR,et al. Emergence of suppressor cells of immunoglobulin synthesis during acute Epstein-Barr virus-induced infectious mononucleosis. J Immunol 123:2095–2101, 1979
Tosato G, Magrath I, Koski I,et al. Activation of suppressor T cells during Epstein-Barr virus induced infectious mononucleosis. N Engl J Med 301:1133–1137, 1979
Rickinson AB, Moss DJ, Pope JH: Long-term T cell-mediated immunity to Epstein-Barr virus in man. II. Components necessary for regression of virus infected leucocyte cultures. Int J Cancer 23:610–617, 1979
Purtilo DT, Bhawan J, Hutt LM,et al. Epstein-Barr virus infections and the X-linked recessive lymphoproliferative syndrome. Lancet 1:798–801, 1978
Provisor AJ, Iacuone JJ, Chilcote RR,et al. Acquired agammaglobulinemia after a life-threatening illness with clinical and laboratory features of infectious mononucleosis in three related male children. N Engl J Med 293:62–65, 1975
Purtilo D, Sakamoto K, Barbanei V,et al. Epstein-Barr virus-induced diseases in boys with the X-linked lymphopro-liferative syndrome (XLP). Am J Med 73:49–56, 1982
Bar RS, DeLor J, Clausen KP,et al. Fatal infectious mononucleosis in a family. N Engl J Med 290:363–367, 1974
Sullivan JL, Byron KS, Brewster FE,et al. X-linked lymphoproliferative syndrome. Natural history of the immunodeficiency. J Clin Invest 71:1765–1778, 1983
Harada S, Sakamoto K, Seeley J,et al. Immune deficiency in the X-linked lymphoproliferative syndrome. J Immunol 129:2532–2535, 1982
Purtilo DT: Immunopathology of X-linked lymphoproliferative syndrome. Immunology Today 4:291–297, 1983
Ballow M, Seeley J, Purtilo DT,et al. Familial Chronic Mononucleosis. Ann Intern Med 6:821–822, 1982
Tobi M, Ravid Z, Feldman-Wess V,et al. Prolonged atypical illness associated with serological evidence of persistent Epstein-Barr virus infection. Lancet 1:62–64, 1982
Zegers BJM, Stoop JW, Reerink-Brongers EE,et al. Serum immunoglobulins in healthy children and adults. Clin Chim Acta 65:319–329, 1975
Graeff de PA, The TH, van Munster PJJ,et al. The primary immune response in patients with selective IgA-deficiency. Clin Exp Immunol 54:778, 1983
Hekker AC, Brand-Saathof B, Vis J,et al. Indirect immunofluorescence for detection of IgM-antibodies to cytomegalovirus. J Infect Dis 140:596–600, 1979
Brand-Saathof B: Detection of IgM-antibodies by indirect immunofluorescence after absorption of serum with anti Fcy (anti IgG). Proceedings 15th Congress of IAMLT, Amsterdam, 1982
Reedman M, Klein G: Cellular localization of an Epstein-Barr virus (EBV)-associated complement fixing antigen in producer and non-producer lymphoblastoid cell lines. Int J Cancer 11:499–520, 1973
Gmelig Meyling F, Dollekamp I, Zegers BJM,et al. Lymphocyte subpopulations in neonates, young children and adults as detected by six surface markers. Acta Paediat Scand 69:13–19, 1980
Tol van MJD, Zijlstra J, Heijnen CJ,et al. Antigen-specific plaque-forming cell response of human cord blood lymphocytes after in vitro stimulation by T cell-dependent antigens. Eur J Immunol 13:390–397, 1983
Dubois R, Meinesz A, Bierhorst-Eilander A,et al. The use of microtitre plates in mixed lymphocytes cultures. Tissue Antigens 4:458–469, 1974
Gmelig Meyling F, UytdeHaag AGCM, Ballieux RE: Human B cell activation in vitro. T cell dependent pokeweed mitogen induced differentiation in blood B lymphocytes. Cell Immunol 33:156–169, 1977
Waldmann TA, Broder SA, Krakauer R,et al. The role of suppressor cells in the pathogenesis of common variable hypogammaglobulinaemia and the immunodeficiency associated with myeloma. Fed Proc 35:2067, 1976
Reed LJ, Muench H: A simple method of estimating fifty per cent end points. Am J Hyg 27:493–497, 1938
Rickinson AB, Rove M, Hart J,et al. T cell mediated regression of spontaneous and of Epstein Barr virus induced B cell transformation in vitro. Studies with cyclosporin A. Cell Immunol 87:646–658, 1984
Krabbe S, Hesse J, Updall P: Primary Epstein-Barr virus infection in early childhood. Arch Dis Childhood 56:49–52, 1981
Gaston JSM, Rickinson AB, Epstein MA: Epstein-Barr virus specific T cell memory in renal allograft recipients under long-term immunosuppression. Lancet 1:923–925, 1982
Tosato G, Straus S, Henle W,et al. Characteristic T cell dysfunction in patients with chronic active Epstein-Barr virus infection (chronic infectious mononucleosis). J Immunol 134:3082–3088, 1985
Virelizier JL, Lenoir R, Griscelli C: Persistent Epstein Barr virus infection in a child with hypergammaglobulinemia and immunoblastic proliferation associated with a selective defect in immune interferon secretion. Lancet 2:231–234, 1978
Morgan DG, Miller G, Niederman JC,et al. Site of Epstein-Barr virus replication in the oropharynx. Lancet 2:1154–1157, 1979
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Kuis, W., Roord, J.J., Zegers, B.J.M. et al. Heterogeneity of immune defects in three children with a chronic active Epstein-Barr virus infection. J Clin Immunol 5, 377–385 (1985). https://doi.org/10.1007/BF00915334
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DOI: https://doi.org/10.1007/BF00915334