11/1/2023 0 Comments Immune repertoire![]() In addition, we reported a transcriptomic meta-analysis of term and preterm mothers and neonates, identifying genetic signatures in preterm neonates associated with spontaneous preterm birth ( 10), and leveraged that signature for drug discovery ( 11). ![]() We recently demonstrated that fetal T cells have a robust, proliferative, and proinflammatory response to maternal Ags, leading to myometrium contractility in cases of PTL, including PPROM, and revealing the fetal immune system as an important contributor to the pathogenesis of PTL ( 8). To further investigate neonatal immunity in the context of PTL, we have focused on the adaptive immune responses in term and preterm neonates and its association with PTL pathogenesis. Whereas many studies have focused on investigating changes associated with maternal immune responses during PTL, recent studies have indicated an important role of the fetal immune system in the pathogenesis of PPROM ( 8, 9). Approximately 70% of PPROM cases are associated with intraamniotic infection, as documented by positive amniotic fluid cultures or by clinical evidence of infection ( 2, 3). Environmental factors (e.g., stress and toxin exposure) and genetic predisposition have also been proposed ( 4– 7). ![]() Several epidemiological and clinical factors are considered precursors to PPROM, including reproductive tract infections, behavioral factors, and obstetric complications ( 4– 6). Despite remarkable improvements in prenatal care over the past three decades, rates of PPROM and subsequent preterm delivery have worsened ( 2). Preterm premature rupture of membranes (PPROM) is a common cause of spontaneous preterm labor (PTL) and is associated with intraamniotic infection in many cases ( 2, 3). Preterm birth (delivery before 37 weeks’ gestational age) is a worldwide clinical concern with ∼15 million cases annually and is the leading cause of neonatal deaths worldwide ( 1). These data provide a detailed analysis of the maternal–fetal immune repertoire in term and preterm patients and contribute to a better understanding of neonate immune repertoire development and potential changes associated with PTL. The higher clonal convergence in PTL could represent mother and fetus both responding to a shared stimulus like an infection. Together, our results suggest the repertoire of preterm infants displays a combination of immature features and convergence with maternal TCR-β clones compared with that of term infants. In preterm pregnancies, we observed significantly higher prevalence of convergent clones between mother/baby pairs than in term pregnancies. Preterm cord blood displayed preferential usage of a number of genes. In cord blood samples, we found that CDR3 lengths correlated with gestational age, with shorter CDR3s in preterm neonates suggesting a less developed repertoire. Both TCR-β and IgH repertoires had shorter CDR3s compared with those in maternal blood. We analyzed TCR β-chain (TCR-β) and IgH diversity, CDR3 lengths, clonal sharing, and preferential usage of variable and joining gene segments. In this study, we analyzed lymphocyte receptor repertoires in maternal and cord blood from 14 term and 10 preterm deliveries, hypothesizing that the high prevalence of infection in patients with PTL may result in specific changes in the T cell and B cell repertoires. Whereas many studies have investigated the maternal immune responses that cause PTL, fetal immune cell activation has recently been raised as an important contributor to the pathogenesis of PTL. Preterm labor (PTL) is the leading cause of neonatal morbidity and mortality worldwide.
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