Brief Report: Decreased JC Virus-Specific Antibody-Dependent Cellular Cytotoxicity in HIV-Seropositive PML Survivors.

BACKGROUND

Progressive multifocal leukoencephalopathy (PML) is an often fatal disease caused by JC virus (JCV) in severely immunocompromised patients, including HIV patients. Development of therapeutics to prevent or treat PML is an urgent medical need. While JCV-specific T cells are crucial to control JCV and recover from PML, the role played by antibodies remains unclear. Anti-JCV antibodies, including potent neutralizing antibodies, can be detected in most infected adults, yet in PML patients, JCV seems to escape from neutralization. Whether antibodies can contribute to JCV control by eliciting Fc-mediated effector functions activity has not been evaluated.

METHODS

We measured the capacity of plasma anti-JCV VP1 antibodies to recruit Fc receptor (FcR)-bearing effector cell functions in 28 HIV patients, comparing subjects without PML with PML survivors (PML S) who were alive 1 year after disease onset or PML progressors (PML P) who succumbed within the first year. Antibody titers against JCV VP1 and HIV gp140 trimer were determined by end-point titer dilution ELISA. FcR-mediated natural killer cell degranulation and IFN-γ production were measured as surrogate for in vitro antibody-dependent cellular cytotoxicity (ADCC).

RESULTS

PML S had higher JCV antibody titers than PML P and patients without PML. However, anti-JCV antibodies had a higher ability to functionally engage FcR in PML P than PML S. Antibody titers and ADCC activity did not vary over time in PML S. Anti-HIV antibody titers and ADCC activity were similar among groups.

CONCLUSIONS

The ability of anti-JCV antibodies to stimulate FcR-bearing effector cell activity might contribute to the outcome of PML. Further studies are warranted to define Fc-mediated functions of anti-JCV antibodies and evaluate whether ADCC can contain JCV replication.