FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV

Autor: Vandana Saxena, Nawaj Shaikh, Sneha Pramod Talathi, Megha Mamulwar, Madhuri Thakar, Sudhanshu Pandey
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
HIV Infections
NK cells
HIV Antibodies
FcγRIIIa-V176F polymorphism
Exon
0302 clinical medicine
Gene Frequency
Viral Envelope Proteins
Genotype
Receptor
Antibody-dependent cell-mediated cytotoxicity
biology
Antibodies
Monoclonal
virus diseases
Middle Aged
Prognosis
Killer Cells
Natural
Treatment Outcome
Infectious Diseases
medicine.anatomical_structure
030220 oncology & carcinogenesis
Female
Immunotherapy
Antibody
ADCC
Research Article
Adult
Adolescent
medicine.drug_class
India
chemical and pharmacologic phenomena
Monoclonal antibody
Polymorphism
Single Nucleotide
lcsh:Infectious and parasitic diseases
Natural killer cell
Young Adult
03 medical and health sciences
Antigen
medicine
Humans
lcsh:RC109-216
FcγRIIIa-Y158H polymorphism
Receptors
IgG
Antibody-Dependent Cell Cytotoxicity
HIV
030104 developmental biology
Immunology
HIV-1
biology.protein
Zdroj: BMC Infectious Diseases, Vol 19, Iss 1, Pp 1-8 (2019)
BMC Infectious Diseases
ISSN: 1471-2334
DOI: 10.1186/s12879-019-4674-z
Popis: Background HIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. However, no data is available on the influence of the polymorphism in FcγRIIIa receptor on HIV-specific ADCC response. Methods The Sanger’s method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed. Results Two polymorphisms: V176F (rs396991) and Y158H (rs396716) were observed. The Y158H polymorphism is reported for the first time in Indian population. Both, V176F (V/V genotype) (p = 0.004) and Y158H (Y/H genotype) (p = 0.032) were found to be significantly associated with higher magnitude of HIV-specific ADCC response. Conclusion The study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection.
Databáze: OpenAIRE
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