Background: Maternal HIV infection can affect placental immunology and expression of the neonatal crystallizable fragment receptor (FcRn), which allows transplacental antibody transfer. This study delineated differences in placental FcRn and T-cell expression by HIV status, with or without viral suppression.
Methods: This observational cohort study in Pune, India, followed pregnant women with and without HIV through 1 year postpartum; 42 had placenta collected, stratified by HIV status. FcRn expression was analyzed by Western blot (normalized by GADPH) and compared using ImageJ. Placental CD4/CD8 abundance was assessed by immunofluorescent counting per high powered field.
Results: The median gestational age at delivery was 38.3 weeks (interquartile range [IQR] 37.5-39.1). Of 18 women living with HIV, all were on combined antiretroviral therapy with a median CD4 of 455 cells/mm (IQR 281-640) at entry and 429 cells/mm (IQR 317-686) at delivery. Ten had undetectable virus (≤40 copies/mL); of those with detectable virus, the median viral load was 151 copies/mL (IQR 118.15-539 334). Relative placental FcRn expression was lower in women living with HIV compared to without (median 0.54 vs 0.84, = .01) and not associated with CD4 or viral load. Women with HIV had significantly higher abundance of placental CD8+ T cells, regardless of viral suppression, compared to women without.
Conclusions: Maternal HIV, even with viral suppression, is associated with lower placental FcRn expression and increased placental CD8+ T cells. These results suggest that dysregulation may not be completely reversed by antiretroviral therapy and could contribute to poorer infant outcomes, even in the absence of mother-to-child HIV transmission.
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http://dx.doi.org/10.1093/ofid/ofaf047 | DOI Listing |
Reprod Toxicol
March 2025
UCB, Cambridge, MA, USA.
To further understand the safety profile of zilucoplan, reproductive toxicology studies in non-human primates (NHPs) were performed, including a male fertility study and a combined embryo-foetal development (EFD) and enhanced pre- and postnatal development (ePPND) study. Human transplacental transfer of zilucoplan was examined in an ex vivo human placental perfusion model of foetal exposure during pregnancy. By comparison with the positive control, a low transfer rate of 0.
View Article and Find Full Text PDFOpen Forum Infect Dis
March 2025
University of Maryland School of Medicine, Baltimore, Maryland, USA.
Background: Maternal HIV infection can affect placental immunology and expression of the neonatal crystallizable fragment receptor (FcRn), which allows transplacental antibody transfer. This study delineated differences in placental FcRn and T-cell expression by HIV status, with or without viral suppression.
Methods: This observational cohort study in Pune, India, followed pregnant women with and without HIV through 1 year postpartum; 42 had placenta collected, stratified by HIV status.
Rev Med Suisse
October 2024
Service d'hématologie, Centre hospitalier universitaire vaudois et Université de Lausanne, 1011 Lausanne.
During pregnancy, the mother's IgG immunoglobulins cross the -placenta via the neonatal Fc receptor (FcRn), enabling the fetus to acquire passive immunity. In the presence of maternal allo- or auto-antibodies, placental transfer of these pathogenic antibodies mediated by FcRn can cause diseases in the fetus and/or the newborn. FcRn blockade therefore appears to be a therapeutic strategy in these high-risk pregnancies, firstly by reducing IgG recycling, -thereby reducing its concentration in the maternal circulation, and secondly by blocking placental transfer.
View Article and Find Full Text PDFAm J Hematol
December 2024
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
MAbs
September 2024
Nonhuman Primate Reagent Resource (NHPRR), Department of Medicine - Innate Immunity, UMass Chan Medical School, Worcester, MA, USA.
Prenatal administration of monoclonal antibodies (mAbs) is a strategy that could be exploited to prevent viral infections during pregnancy and early life. To reach protective levels in fetuses, mAbs must be transported across the placenta, a selective barrier that actively and specifically promotes the transfer of antibodies (Abs) into the fetus through the neonatal Fc receptor (FcRn). Because FcRn also regulates Ab half-life, Fc mutations like the M428L/N434S, commonly known as LS mutations, and others have been developed to enhance binding affinity to FcRn and improve drug pharmacokinetics.
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