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Hepatitis B Virus-infected Pregnant Females with Higher Circulating HBsAg

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Ashish Kumar Vyas, Pooja Negi    06 December 2018

Hepatitis B Virus-infected Pregnant Females with Higher Circulating HBsAg Levels Showed Impaired Immune Imprint in Their Newborns at Birth

Ashish Kumar Vyas, Pooja Negi, Sharda Patra, Jaswinder Singh Maras, Shiv Kumar Sarin, Nirupma Trehanpati: Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, Obstetrics and Gynecology, Lady Harding Medical College, New Delhi

Background: Vertical transmission of hepatitis B virus (HBV) from infected mother to the newborn often results in viral persistence. To understand mechanisms of materno-fetal HBV transmission and viral persistence, we studied maternal immunity and peri pheral blood mononuclear cell (PBMC) transcriptome in mothers and newborns.

Methods: Fifty HBsAg positive mothers and babies were included; 22 with the transmission (Gr. I, T, n =22) and 28 with no transmission (Gr. II, NT, n =28) to the new - borns, and compared with healthy mother -baby pairs (Gr. III, n=10). PBMCs were analyzed for HBV-specific D Cs, T cells, T follicular helper (TFh), B cells and functional immune responses, cytokine levels as well as transcriptome signatures to identify immune gene expression correlates for protective immunity.

Results: Group II mothers had lower HBsAg levels (3.82 x103 vs. 1.493x104, p<0.0001) with greater HBV specific responses of DCs, T cells, TFh and B cell than Gr. I mothers. The percentage frequencies of TFh cells had lower (11.06±1.71 vs. 18.05±1.74, p =0.02) in Gr. I mothers was accompanied with reduced I L21 (356.1±50.17 vs. 493.6±56.70, p =0.04) levels. TFh frequencies and IL21 levels inversely correlated with HBV DNA levels. The cut-off level of 9.5% and 8.93% from the receiver operating curve predicted the involvement of TFh and B cells in HBV transmission. Transcriptome signatures revealed that maternal gene imprints were reflected in their new-borns. Further genes related to DCs, TFH and B cells and were increased in Gr. II. HBsAg+ve newborns showed a boost in cellular and humoral responses after vaccination.

Conclusion: In HBV infected mothers, low serum IL-21 levels, decreased TFh and plasma B cell frequencies are associated with vertical transmission of HBV to new-born. These features are indicative of low protective immunity.

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