To the Editor:
Epidemiologic evidence strongly suggests that young adult Hodgkin's disease (YAHD) is a rare sequelum of a late (adolescence or young adulthood) infection with a common childhood virus, analogous to the appearance of paralysis after natural infection with poliovirus.1 Although Epstein-Barr virus (EBV) is considered the leading candidate as the putative causal virus, current evidence is inconclusive. EBV DNA has been demonstrated in Hodgkin's tumors, but is much less prevalent in tumors from young adult cases or cases of the nodular sclerosis type.2 If EBV does play an etiologic role, there is likely to be a cofactor, possibly another virus.
KSHV (Kaposi's Sarcoma Associated Herpes Virus or Human Herpes Virus 8), like EBV, is a gamma Herpes virus, with sequence homology to EBV. It was first isolated from Kaposi's sarcoma tumor tissue3and subsequently from tumor tissue and peripheral blood mononuclear cells from patients with body cavity lymphomas,4Castleman's disease,4 and multiple myeloma (in bone marrow stromal cells only).5 Ninety percent of Kaposi's sarcoma patients and 11% of human immunodeficiency virus-negative adult blood donors are positive for KSVH antibody.6 Although a few cases of Hodgkin's disease have been evaluated for evidence of this virus (with negative results), neither age at diagnosis nor histologic type was specified.4,5
We examined serum from 39 twin pairs with Hodgkin's disease diagnosed before age 50, plus 46 controls, to assess the seroprevalence of KSHV antibody in YAHD patients. Subjects were recruited from the International Twin Study, a large registry developed by advertising for twins with chronic disease. Three twin pairs were concordant for YAHD and 36 were discordant, totaling 42 YAHD cases (60% nodular sclerosis, 12% mixed cellularity, 5% lymphocyte predominant, 2% lymphocyte depleted, 7% not otherwise specified, and 14% unknown histology). Thirty-six healthy twins of cases were also tested. Controls comprised spouses or friends of either member of the twin pair (38), two healthy identical twin pairs (4), and laboratory staff (2). Forty-six percent of the twin pairs were male and 54% were female; 48% of controls were male and 52% were female. Laboratory investigators were blinded with respect to the identity of the case, cotwin, and control.
KSHV-IgG antibody was measured from thawed frozen serum using whole viral lysate containing the majority of the KSHV structural proteins in an enzyme-linked immunosorbent assay. Serum from 92 Kaposi's sarcoma patients gathered in a population-based case-control study were analyzed simultaneously as an internal control for the assay. One YAHD case and one control were each positive for KSVH antibody, at the lowest detectable concentration (0.05 to 0.20), giving a prevalence in cases and controls of 2%. Both the case and the control were male. None of the 36 healthy twins of YAHD cases was positive. In contrast, 40 of the 92 KS sera were positive for KSVH antibody (44%).
KSHV antibody was not detectable in any substantial number of YAHD cases. Thus, it appears that KSHV does not play a role in the etiology of YAHD, and the search to identify the etiologic agent of YAHD must continue.
Support for this project was provided by National Institutes of Health Grants No. CA58839 and UO1 CA66533.