Pahwa Prabhjyoti, Vyas Ashish Kumar, Sevak Jayesh Kumar, Singh Ravinder, Maras Jaswinder Singh, Patra Sharda, Sarin Shiv K, Trehanpati Nirupama
Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
Department of Obstetrics and Gynaecology, Lady Harding Medical College, New Delhi, India.
J Reprod Immunol. 2024 Mar;162:104208. doi: 10.1016/j.jri.2024.104208. Epub 2024 Jan 28.
High HBV DNA levels predispose to mother to child transmission (MTCT) of HBV. Early nucleotide analogue (NA) therapy can reduce HBV DNA and minimize MTCT. We analysed immune-metabolic profile in pregnant mothers who received NA from 2nd trimester compared with untreated mothers. In 2nd trimester, there was no difference in immune profiles between Gr.1 and Gr.2 but high viral load women had downregulated pyruvate, NAD+ metabolism but in 3rd trimester, Gr.1 had significant reduction in HBV-DNA, upregulated pyruvate and NAD with increased IFN-2αA, CD8Tcells, NK cells and decreased Tregs, IL15, IL18, IL29, TGFβ3 compared to Gr.2. In Gr.1, three eAg-ve women showed undetectable DNA and HBsAg. At delivery, Gr.1 showed no MTCT, with undetectable HBV DNA, HBsAg, high CD8 and NK cells in two women. We conclude, that starting NA from second trimester, reduces HBV load and MTCT, modulates NAD, induces immunity and suggest use of NA in early gestation in future trials.
高乙肝病毒脱氧核糖核酸(HBV DNA)水平易导致乙肝病毒母婴传播(MTCT)。早期核苷酸类似物(NA)治疗可降低HBV DNA水平并使MTCT风险降至最低。我们分析了孕中期开始接受NA治疗的孕妇与未治疗孕妇的免疫代谢特征。在孕中期,第1组和第2组的免疫特征没有差异,但病毒载量高的女性丙酮酸、烟酰胺腺嘌呤二核苷酸(NAD+)代谢下调;而在孕晚期,与第2组相比,第1组的HBV-DNA显著降低,丙酮酸和NAD上调,干扰素-2αA、CD8+T细胞、自然杀伤细胞(NK细胞)增加,调节性T细胞(Tregs)、白细胞介素15(IL15)、白细胞介素18(IL18)、白细胞介素29(IL29)、转化生长因子β3(TGFβ3)减少。在第1组中,3名e抗原阴性女性的DNA和乙肝表面抗原(HBsAg)检测不到。分娩时,第1组未出现MTCT,两名女性的HBV DNA、HBsAg检测不到,CD8+和NK细胞水平较高。我们得出结论,孕中期开始使用NA可降低HBV载量和MTCT,调节NAD,诱导免疫,并建议在未来试验中在妊娠早期使用NA。