JC Virus-Specific Immune Responses in Human Immunodeficiency Virus Type 1 Patients with Progressive Multifocal Leukoencephalopathy

Abstract

Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease caused by uncontrolled polyomavirus JC (JCV) in severely immunodeficient patients. We investigated the JCV-specific cellular and humoral immunity in the Swiss HIV Cohort Study. We identified PML cases ( n = 29), as well as three matched controls per case ( n = 87), with prospectively cryopreserved peripheral blood mononuclear cells and plasma at diagnosis. Nested controls were matched according to age, gender, CD4 + T-cell count, and decline. Survivors ( n = 18) were defined as being alive for >1 year after diagnosis. Using gamma interferon enzyme-linked immunospot assays, we found that JCV-specific T-cell responses were lower in nonsurvivors than in their matched controls ( P = 0.08), which was highly significant for laboratory- and histologically confirmed PML cases ( P = 0.004). No difference was found between PML survivors and controls or for cytomegalovirus-specific T-cell responses. PML survivors showed significant increases in JCV-specific T cells ( P = 0.04) and immunoglobulin G (IgG) responses ( P = 0.005). IgG responses in survivors were positively correlated with CD4 + T-cell counts ( P = 0.049) and negatively with human immunodeficiency virus RNA loads ( P = 0.03). We conclude that PML nonsurvivors had selectively impaired JCV-specific T-cell responses compared to CD4 + T-cell-matched controls and failed to mount JCV-specific antibody responses. JCV-specific T-cell and IgG responses may serve as prognostic markers for patients at risk.