Journal article
Decreased JC Virus-Specific Antibody-Dependent Cellular Cytotoxicity in HIV-Seropositive PML Survivors
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol.82(2), pp.220-224
10/01/2019
DOI: 10.1097/QAI.0000000000002105
PMCID: PMC7179760
PMID: 31513076
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 endpoint titer dilution ELISA. FcR-mediated natural killer cell degranulation and IFN-gamma 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.
Details
- Title: Subtitle
- Decreased JC Virus-Specific Antibody-Dependent Cellular Cytotoxicity in HIV-Seropositive PML Survivors
- Creators
- Chen S. Tan - Beth Israel Deaconess Medical CenterJoshua Ghofrani - Beth Israel Deaconess Medical CenterEmma Geiger - Beth Israel Deaconess Medical CenterIgor J. Koralnik - Rush University Medical CenterStephanie Jost - Beth Israel Deaconess Medical Center
- Resource Type
- Journal article
- Publication Details
- JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol.82(2), pp.220-224
- DOI
- 10.1097/QAI.0000000000002105
- PMID
- 31513076
- PMCID
- PMC7179760
- NLM abbreviation
- J Acquir Immune Defic Syndr
- ISSN
- 1525-4135
- eISSN
- 2331-6993
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 5
- Grant note
- K02NS097146 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R01AI116363 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01 AI116363 / NIH NIAID; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) K02 NS097146; R01 NS047029; R01 NS074995 / NIH NINDS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Language
- English
- Date published
- 10/01/2019
- Academic Unit
- Iowa Neuroscience Institute; Internal Medicine
- Record Identifier
- 9984366278102771
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