98%
921
2 minutes
20
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.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879550 | PMC |
http://dx.doi.org/10.1093/ofid/ofaf047 | DOI Listing |
PLoS Pathog
August 2025
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.
Maternal antibodies serve as a temporary form of inherited immunity, providing humoral protection to vulnerable neonates. Whereas IgG is actively transferred up a concentration gradient via the neonatal Fc Receptor (FcRn), maternal IgA and IgM are typically excluded from fetal circulation. Further, not all IgG molecules exhibit the same transfer efficiency, being influenced by subclass, Fab and Fc domain glycosylation, antigen-specificity, and the temporal dynamics of maternal antibody responses.
View Article and Find Full Text PDFJ Pharm Sci
July 2025
Department of Pharmacy, The First Affiliated Hospital of Fujian Medical University, 20 Cha Zhong M. Rd, Fuzhou 350005, China; Department of Pharmacy, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. Electronic address: Fsnowi
The placenta serves as a critical interface for maternal-fetal substance exchange, including the active transport of immunoglobulin G (IgG), which is essential for neonatal immune protection. While mechanisms of IgG transfer are well-studied, the impact of therapeutic monoclonal antibodies (mAbs) on placental IgG dynamics during pregnancy remains unclear. This study aimed to predict maternal and fetal drug concentrations of ustekinumab (UST), an IgG1 monoclonal antibody used for treating inflammatory bowel disease (IBD), using a physiologically based pharmacokinetic (PBPK) model.
View Article and Find Full Text PDFImmunol Rev
May 2025
Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore.
Immunoglobulin E (IgE) is the most recently discovered and evolved mammalian antibody type, best known for interacting with mast cells (MCs) as immune effectors. IgE-mediated antigen sensing by MC provides protection from parasites, venomous animals, bacteria, and other insults to barrier tissues exposed to the environment. IgE and MCs act as inflammation amplifiers and immune response adjuvants.
View Article and Find Full Text PDFClin Pharmacol Ther
August 2025
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Therapeutic antibodies are often prescribed off-label to pregnant patients to treat inflammatory, autoimmune, or malignant conditions. Despite their broad use, the extent of fetal exposure to such therapeutic antibodies and the risk to fetal development remain largely unknown. Given the ethical challenges to conduct randomized trials in pregnant patients, modeling and simulation approaches offer an opportunity to yield mechanistic insights using data from observational studies.
View Article and Find Full Text PDFReprod Toxicol
May 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 PDF