Antibodies to JC and BK viruses among persons with non-Hodgkin lymphoma

Two related polyomaviruses, JC virus (JCV) and BK virus (BKV), commonly cause lifelong infections in humans, with periodic reactivation manifesting as viral shedding in urine. Because JCV can infect lymphocytes and cause chromosomal damage, it is a plausible candidate to cause non-Hodgkin lymphoma (NHL). To test this hypothesis, we measured IgG antibodies to JCV and BKV capsids using a virus-like particle enzyme immunoassay in 3 separate groups of subjects. First, in a U.S. population-based case-control study of NHL (724 cases, 622 controls), we found lower JCV antibody levels in cases than controls (median optical density = 0.12 vs. 0.21, p < 0.0001); likewise, JCV seroprevalence was lower in cases (49% vs. 59%, adjusted odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.56-0.87). In contrast, BKV antibody levels did not differ between groups. Second, we found that JCV and BKV antibody levels changed little over time among 24 NHL patients receiving chemotherapy. Third, we evaluated 126 homosexual men, of whom 46 were shedding JCV and 14 were shedding BKV in urine. Antibody levels were much higher in shedders than non-shedders (JCV: median optical density = 0.67 vs. 0.07, p < 0.0001; BKV: 0.87 vs. 0.40, p = 0.003), indicating that these antibodies are a marker for viral replication. Because no deficit of BKV antibody was seen in NHL cases, and because antibody levels did not change materially with chemotherapy, we suggest that the lower levels of JCV antibody observed in NHL patients may not be due entirely to a disease or treatment effect. Additional research is needed to determine whether JCV replication is decreased in individuals with NHL and whether these findings are consistent with an etiologic role for JCV in NHL.