Poster Presentation Lorne Infection and Immunity 2023

An unbiased analysis of neonatal immune cell characteristics to discover novel biomarkers that predict the risk of neonatal sepsis (#148)

Srushti M Kasare 1 2 3 , Simone S Schüller 1 2 3 , Peter Richmond 2 3 4 , Andrew Currie 2 5 , Tobias Strunk 1 2 3
  1. Neonatal Directorate, King Edward Memorial Hospital, Perth, Western Australia, Australia
  2. Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Western Australia, Australia
  3. School of Medicine, University of Western Australia, Perth, Western Australia, Australia
  4. Department of Immunology, Perth Children’s Hospital, Perth, Western Australia, Australia
  5. Medical, Molecular and Forensic Sciences, Murdoch University, Perth, Western Australia, Australia

Worldwide 15 million infants each year are born preterm and 1.3 million infants suffer from sepsis, a life-threatening bacterial bloodstream infection. Preterm infants are susceptible to sepsis and this is highly dependent on gestational age (GA) and most frequent during the neonatal period (28 days from birth). Infants who survive may suffer permanent disabilities due to organ damage resulting from either the infection itself or from the inflammatory responses. Despite established epidemiological and clinical risk factors for sepsis in preterm infants, the developmental maturation events of preterm immune system remain largely understudied.

One of the greatest challenges is to collect longitudinal samples from the neonates for immune cell analysis. The presentation will highlight results of a prospective observational study which recruited 129 very preterm infants (<30 weeks GA) of which 43 developed late-onset sepsis (LOS), and 20 healthy term infants born at King Edward Memorial Hospital, Perth, Australia. This study used seven colour flow cytometry to characterise peripheral blood innate cells (monocytes and dendritic) and adaptive T lymphocytes (regulatory T cells and δγT cells) at days of life 1, 7, 14, 21, and 28. The methods for flow cytometry data analysis included traditional manual gating and automated gating (clustering and dimensionality reduction) to overcome the risk of bias associated with traditional method.  

The results from this study will provide vital information on the differences in characteristics of immune cells of preterm infants compared to term infants. Furthermore, the developmental trends of immune cells will be compared between sepsis and no-sepsis preterm infants. The findings will provide the foundation for larger studies for targeted immune therapeutics that will globally reduce the occurrence of sepsis in neonates.

 

  1. Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, et al. Global, regional, and national causes of under-5 mortality in 2000–15: an updated systematic analysis with implications for the Sustainable Development Goals. The Lancet. 2016;388(10063):3027-35.
  2. Fleischmann C, Reichert F, Cassini A, Horner R, Harder T, Markwart R, et al. Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis. Archives of Disease in Childhood. 2021;106(8):745-52.
  3. El Hassani SEM, Berkhout DJ, Niemarkt HJ, Mann S, De Boode WP, Cossey V, et al. Risk factors for late-onset sepsis in preterm infants: a multicenter case-control study. Neonatology. 2019;116(1):42-51.
  4. Chawanpaiboon S, Vogel JP, Moller AB, Lumbiganon P, Petzold M, Hogan D, et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob Health. 2019;7(1):e37-e46.
  5. Amir E-aD, Davis KL, Tadmor MD, Simonds EF, Levine JH, Bendall SC, et al. viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nature biotechnology. 2013;31(6):545-52.
  6. Yu N, Li X, Song W, Li D, Yu D, Zeng X, et al. CD4+ CD25+ CD127low/− T cells: a more specific Treg population in human peripheral blood. Inflammation. 2012;35(6):1773-80.
  7. De Jong E, Strunk T, Burgner D, Lavoie PM, Currie A. The phenotype and function of preterm infant monocytes: implications for susceptibility to infection. Journal of leukocyte biology. 2017;102(3):645-56.