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Perinatal HIV-1 transmission: Fc gamma receptor variability associates with maternal infectiousness and infant susceptibility.
- Source :
- Retrovirology; 6/10/2016, Vol. 13, p1-16, 16p
- Publication Year :
- 2016
-
Abstract
- Background: Accumulating data suggest that immune effector functions mediated through the Fc portion of HIV-1-specific immunoglobulin G (IgG) are a key component of HIV-1 protective immunity, affecting both disease progression and HIV-1 acquisition. Through studying Fc gamma receptor (Fc?R) variants known to alter IgG Fc-mediated immune responses, we indirectly assessed the role of Fc?R-mediated effector functions in modulating perinatal HIV-1 transmission risk. In this study, genotypic data from 79 HIV-1 infected mothers and 78 HIV-1 infected infants (transmitting cases) were compared to 234 HIV-1 infected mothers and 235 HIV-1 exposed-uninfected infants (non-transmitting controls). Associations, unadjusted and adjusted for multiple comparisons, were assessed for overall transmission and according to mode of transmission—intrapartum (n = 31), in utero (n = 20), in utero-enriched (n = 48). Results: The maternal FcγRIIIa-158V allele that confers enhanced antibody binding affinity and antibody-dependent cellular cytotoxicity capacity significantly associated with reduced HIV-1 transmission [odds ratio (OR) 0.47, 95 % confidence interval (CI) 0.28-0.79, P = 0.004; P<subscript>Bonf</subscript> > 0.05]. In particular, the FcγRIIIa-158V allele was underrepresented in the in utero transmitting group (P = 0.048; P<subscript>Bonf</subscript> > 0.05) and in utero-enriched transmitting groups (P = 0.0001; P<subscript>Bonf</subscript> < 0.01). In both mother and infant, possession of an FcγRIIIb-HNA1b allotype that reduces neutrophil-mediated effector functions associated with increased transmission (OR 1.87, 95 % CI 1.08-3.21, P = 0.025; P<subscript>Bonf</subscript> > 0.05) and acquisition (OR 1.91, 95 % CI 1.11-3.30, P = 0.020; P<subscript>Bonf</subscript> > 0.05), respectively. Conversely, the infant FcγRIIIb-HNA1a∣1a genotype was significantly protective of perinatal HIV-1 acquisition (OR 0.42, 95 % CI 0.18-0.96, P = 0.040; P<subscript>Bonf</subscript> > 0.05). Conclusions: The findings of this study suggest a potential role for FcγR-mediated effector functions in perinatal HIV-1 transmission. However, future studies are required to validate the findings of this study, in particular associations that did not retain significance after adjustment for multiple comparisons. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17424690
- Volume :
- 13
- Database :
- Complementary Index
- Journal :
- Retrovirology
- Publication Type :
- Academic Journal
- Accession number :
- 116202974
- Full Text :
- https://doi.org/10.1186/s12977-016-0272-y