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Brief Report

Decreased JC Virus-Specific Antibody-Dependent Cellular Cytotoxicity in HIV-Seropositive PML Survivors

Tan, Chen S. MDa,b; Ghofrani, Joshua BSb; Geiger, Emma BSb; Koralnik, Igor J. MDc; Jost, Stephanie PhDb

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1, 2019 - Volume 82 - Issue 2 - p 220–224
doi: 10.1097/QAI.0000000000002105
Translational Research
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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.

aDivision of Infectious Diseases;

bDepartment of Medicine, Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston MA; and

cDepartment of Neurology, Rush University Medical Center, Chicago, IL.

Correspondence to: Chen S. Tan, MD, Beth Israel Deaconess Medical Center, E/CLS 1011 330, Brookline Avenue, Boston, MA 02215 (e-mail: ctan@bidmc.harvard.edu).

Supported by NIH NINDS K02 NS097146, R01 NS047029, R01 NS074995, and NIH NIAID R01 AI116363.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).

Received February 25, 2019

Accepted May 06, 2019

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.