Active tuberculosis disease in pregnancy alters frequencies of B-cell subsets among exposed neonates in Uganda

Maternal tuberculosis (TB) remains a significant risk factor for compromising infant immune development in high-burden TB disease settings. The integrity of B-cells in early life is important for the development of immediate and long-term immunity in infants. This study assessed circulating B-cell subset frequencies in babies born to mothers with and without active TB in Uganda. A cohort of 46 mother-infant pairs (24 cases, 22 controls) was recruited between September 2021 and July 2022 from three health facilities in Kampala. Infant cases were born to mothers with active TB, whereas infant controls were born to mothers without active TB. Peripheral blood mononuclear cells (PBMCs) were collected and processed from infants at baseline (≤ 1 month of age), and at three months and six months. PBMCs were stained with a 15-marker B-cell panel for spectral flow cytometry. Data were analysed using FlowJo and R v4.4.3. Mixed-effects modelling was applied for statistical testing, with time point as a fixed effect and participant as a random effect. Post-hoc comparisons used estimated marginal means. At baseline, infant cases were associated with decreased mean circulating frequencies of total B cells (18.5 versus 30.2; p = 0.02), naïve B cells (55.1 versus 68.9; p = 0.01), and mature B cells (43.6 versus 66.5; p = 0.03) compared to infant controls. Additionally, the infant cases were associated with increased baseline immature (56.4 versus 33.4; p = 0.03) and antibody-secreting B cells (15.6 versus 10.5; p = 0.04) compared to infant controls. No differences were observed at three or six months, except for IgG-only memory B cells, which were increased among infant cases at six months (14.4 versus 8.3; p = 0.04). Exposure to Mycobacterium tuberculosis in utero may decrease the preimmune B-cell repertoire in early life, potentially increasing the risk of neonatal infections and altered responses to routine infant vaccines. Prompt diagnosis and treatment of TB during pregnancy are therefore crucial to prevent poor neonatal morbidity and mortality in our setting.