HIV-related Differences in Placental Immunology: Data From the PRACHITi Cohort in Pune, India

与 HIV 相关的胎盘免疫学差异:来自印度浦那 PRACHITi 队列的数据

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作者:Jyoti S Mathad, Mallika Alexander, Ramesh Bhosale, Shilpa Naik, Lisa Marie Cranmer, Vandana Kulkarni, Sydney Busch, Andrea Chalem, Emily Gitlin, Jun Lei, Anguo Liu, Jin Liu, Yang Liu, Rupak Shivakoti, Amita Gupta, Irina Burd

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.

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.

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/mm3 (IQR 281-640) at entry and 429 cells/mm3 (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, P = .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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