Heterogeneity of immune defects in three children with a chronic active Epstein-Barr virus infection

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.

Severe chronic active Epstein-Barr virus infection syndrome

“…However, Kuis et al reported that one patient exhibited normal cytotoxicity, whereas a second patient exhibited no EBV-specific cytotoxicity and unusually high levels of virus-infected B cells in the peripheral blood and the affected lymph node (15). As mentioned earlier, some patients with SCAEBV fail to make antibodies to EBNA 1, suggesting some defect in the immunosurveillance of EBV infection, a cellular alteration, or a mutation elsewhere in the viral genome (5,17,18).…”

“…Rather, various heterogeneous immune defects, such as defective immune interferon secretion, low NK cell activity, low mitogen stimulation of peripheral blood lymphocytes, and an inverted or increased CD4/CD8 ratio, have been reported. Low NK cell and antibody-depen-9 dent cell-mediated cytotoxicity activities and inverted CD4/CD8 ratio 3 Circulating immune complexes and 15 inverted CD4/CD8 ratio 4 Circulating immune complexes and 15 no EBV cytotoxicity 5 Low mitogen stimulation response 15 6 Inverted CD4/CD8 ratio 24 7 Inverted CD4/CD8 ratio 24 13 Low NK cell activity 19a 15 Low NK cell activity 12 21 Low NK cell activity and increased 21,22 CD4/CD8 ratio 22 Increased CD4/CD8 ratio 14 23 Increased CD4/CD8 ratio 7 26 Inverted CD4/CD8 ratio 22…”

“…Acyclovir, a potent antiherpesvirus agent which is useful for treating some transplant recipients with life-threatening EBV-induced polyclonal lymphoproliferative disease, has no significant clinical effect in patients with SCAEBV (15,21,22). However, some success with recombinant interleukin-2 treatment has been reported (12).…”

Autologous Epstein-Barr virus (EBV)–specific cytotoxic T cells for the treatment of persistent active EBV infection

“…[4][5][6][7] The pathogenesis and etiology of CAEBV syndrome are not well characterized, and it is not clear whether the defect lies in the virus or in the host response. [13][14][15] This lack of information has hampered the development of effective therapies. Sporadic clinical improvements have been reported after infusion of interleukin 2 (IL-2), high-dose immunoglobulin, antiviral drugs, or steroids, but these results have been hard to replicate.…”

Treatment of EBV driven lymphoproliferation with erythrophagocytosis: 12 year follow up

“…In patients with X-linked lymphoproliferative syndrome and those with other primary immunodeficiencies the development of VAHS is often fatal. [16][17][18][19] The use of interferon is well established in the treatment of several viral infections, including hepatitis B and C. 20 21 It has also been used to shorten EBV excretion in renal transplant recipients, 22 and some success has been reported in EBV driven post-transplant lymphoproliferative disease. 23 The use of interferon in a patient with CVID and chronic EBV infection has been described previously 9 ; however, the patient described in that study was not reported as having evidence of VAHS.…”