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Longitudinal assessment of immune development in preterm babies

Presented at the Neonatal Society 2018 Spring Meeting (programme).

Kamdar S, Hutchinson R, Laing A, Stacey F, Fleming P, Gibbons D

Department of Immunobiology, Kings College London, Guys Hospital, London Bridge, London, SE1 9RT, UK
Blizard Institute, Barts and the London School of Medicine and Dentistry, London E1 2AT, UK
Homerton University Hospital NHS Foundation Trust, Homerton Row, London, E9 6SR, UK

Background: The increased susceptibility of preterm infants to infection has, in part, been attributed to an immature immune system. However, we previously demonstrated that neonatal T cells (even from those born prematurely) are surprisingly capable of anti-inflammatory functions via their production of the chemokine and neutrophil activator, CXCL8. We hypothesise that the preterm immune system may not be as ‘defective’ as once thought and have assessed the whole immune profile of infants born prematurely over the first few months of life.

Methods: Longitudinal peripheral blood samples were obtained with parental consent and ethical approval from preterm babies (23+6 - 30+6 weeks’ gestational age) from birth until 36 weeks corrected gestational age. Additional blood samples were taken during episodes of suspected infection. PBMCs were extracted by ficoll gradient centrifugation and phenotyped for 117 different cell populations by flow cytometry. These included different T cells, B cells, monocytes and NK cells and the cytokines they produced, that together made up the immune landscape of the individual infants. The project was funded by research grants from Barts Charity and CRUK.

Results: Our initial results (from a total of 30 infants) provide a longitudinal assessment of the developing immune system with advancing postnatal adaptation and age. Interestingly, the immune landscape among preterm babies with an uncomplicated postnatal course (n=10) becomes stable very soon after birth, maturing with days of life irrelevant of gestational age at birth. This contrasts with those born to mothers with chorioamnionitis (n=10) and those with a less stable postnatal course (n=10) where we see increased activation of innate cells such as NK cells and gd T cells with increased cytokine production post stimulation. Interestingly, the ability of T cells to produce CXCL8 is reduced in these less stable babies.

Conclusion: These data show that environmental factors alter the immune status of stable infants immediately post birth in a similar way independent of gestational age at birth. This is, however, different in sick infants, where the immune profile is very varied. These data provide new insights into the function of the preterm immune system and its postnatal adaptation and suggests that the loss of anti-microbial CXCL8-producing cells may be detrimental.

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