Perinatal HIV-1 transmission : Fc gamma receptor variability associates with maternal infectiousness and infant susceptibility
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 (FcγR) variants known to alter IgG Fc-mediated immune responses, we indirectly assessed the role of FcγR-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; PBonf > 0.05]. In particular, the FcγRIIIa-158V allele was underrepresented in the in utero transmitting group (P = 0.048; PBonf > 0.05) and in utero-enriched transmitting groups (P = 0.0001; PBonf < 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; PBonf > 0.05) and acquisition (OR 1.91, 95 % CI 1.11-3.30, P = 0.020; PBonf > 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; PBonf > 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Retrovirology - 13(2016), 1 vom: 10. Juni, Seite 40 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lassaunière, Ria [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.05.2017 Date Revised 13.11.2018 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12977-016-0272-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM261281267 |
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| 100 | 1 | |a Lassaunière, Ria |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Perinatal HIV-1 transmission |b Fc gamma receptor variability associates with maternal infectiousness and infant susceptibility |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 02.05.2017 | ||
| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 (FcγR) variants known to alter IgG Fc-mediated immune responses, we indirectly assessed the role of FcγR-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) | ||
| 520 | |a 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; PBonf > 0.05]. In particular, the FcγRIIIa-158V allele was underrepresented in the in utero transmitting group (P = 0.048; PBonf > 0.05) and in utero-enriched transmitting groups (P = 0.0001; PBonf < 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; PBonf > 0.05) and acquisition (OR 1.91, 95 % CI 1.11-3.30, P = 0.020; PBonf > 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; PBonf > 0.05) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Alleles | |
| 650 | 4 | |a Antibody-dependent cell cytotoxicity | |
| 650 | 4 | |a HIV-1 | |
| 650 | 4 | |a IgG receptors | |
| 650 | 4 | |a Phagocytosis | |
| 650 | 4 | |a Risk factors | |
| 650 | 4 | |a Vertical infectious disease transmission | |
| 650 | 7 | |a HIV Antibodies |2 NLM | |
| 650 | 7 | |a Immunoglobulin G |2 NLM | |
| 650 | 7 | |a Receptors, IgG |2 NLM | |
| 700 | 1 | |a Musekiwa, Alfred |e verfasserin |4 aut | |
| 700 | 1 | |a Gray, Glenda E |e verfasserin |4 aut | |
| 700 | 1 | |a Kuhn, Louise |e verfasserin |4 aut | |
| 700 | 1 | |a Tiemessen, Caroline T |e verfasserin |4 aut | |
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