Article ; Online: Brief Report: Decreased JC Virus-Specific Antibody-Dependent Cellular Cytotoxicity in HIV-Seropositive PML Survivors.
Journal of acquired immune deficiency syndromes (1999)
2019 Volume 82, Issue 2, Page(s) 220–224
Abstract: 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. ...
| Abstract | 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. |
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| MeSH term(s) | Adult ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Antibody-Dependent Cell Cytotoxicity/immunology ; Capsid Proteins/immunology ; Female ; HIV Infections/immunology ; Humans ; JC Virus/immunology ; Leukoencephalopathy, Progressive Multifocal/immunology ; Male ; Middle Aged ; env Gene Products, Human Immunodeficiency Virus/immunology |
| Chemical Substances | Antibodies, Viral ; Capsid Proteins ; VP1 protein, polyomavirus ; env Gene Products, Human Immunodeficiency Virus ; gp140 envelope protein, Human immunodeficiency virus 1 |
| Language | English |
| Publishing date | 2019-09-12 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, N.I.H., Extramural |
| ZDB-ID | 645053-2 |
| ISSN | 1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135 |
| ISSN (online) | 1944-7884 ; 1077-9450 |
| ISSN | 0897-5965 ; 0894-9255 ; 1525-4135 |
| DOI | 10.1097/QAI.0000000000002105 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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