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BMC Infect Dis ; 19(1): 1053, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842762

RESUMO

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.


Assuntos
Citotoxicidade Celular Dependente de Anticorpos/genética , Infecções por HIV/genética , Infecções por HIV/imunologia , HIV-1/imunologia , Células Matadoras Naturais/imunologia , Polimorfismo de Nucleotídeo Único/genética , Receptores de IgG/genética , Adolescente , Adulto , Anticorpos Monoclonais/uso terapêutico , Feminino , Frequência do Gene/genética , Genótipo , Anticorpos Anti-HIV/uso terapêutico , Infecções por HIV/terapia , Humanos , Imunoterapia , Índia , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento , Proteínas do Envelope Viral/farmacologia , Adulto Jovem
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