Brief report: killer cell defect and persistent immunological abnormalities in two patients with chronic active...

Two members of a family have manifested a syndrome of chronic active Epstein-Barr virus (EBV) infection. A father and his daughter suffered prolonged or recurrent mononucleosis, with splenomegaly, anemia, and intermittent fever; persistent immunological abnormalities included defective natural killer (NK) cytotoxicity, inverted CD4/CD8 ratios, hyper IgG1, high EBV viral capsid antigen (VCA) and early antigen (EA) antibodies, and low or undetectable EBV nuclear antigen (EBNA) antibody titers. The EBV seronegative member of the family was free of these abnormalities. However, NK activity in the seronegative individual was low-normal and its EBV-specific antibody-dependent K-cell cytotoxicity (EBV-ADCC) was abnormally low, suggesting that this K-NK cell defect may be primary. The father, who suffered from the syndrome for more than 15 years, lacked (or lost) antibodies to EBV-envelope and infected cell membranes, such as antibody-dependent cellular cytotoxicity (ADCC), neutralizing (NT), and gp 350/220 antibodies. Slow improvement over a period of years was heralded by rising NK cytotoxicity.