Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Dried blood spot samples as a diagnostic and prognostic tool for neonatal sepsis in preterm infants (#606)

Azra Karamehmedovic 1 2 , Julie Hibbert 3 , Duc Ninh Nguyen 4 , Andrew Currie 5 6 , Per T. Sangild 4 , Allan Stensballe 1
  1. Department of Health Science and Technology, Aalborg University, Aalborg, Denmark
  2. Sino-Danish Center for Education and Research, University of Chinese Academy Sciences, Beijing, China
  3. Centre for Neonatal Research & Education and Division of Paediatrics, University of Western Australia, Perth, Australia
  4. Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark
  5. Centre for Neonatal Research & Education, University of Western Australia, Perth, Australia
  6. Medical and Molecular Sciences, School of Veterinary and Life Sciences, Murdoch University, Perth, Australia

Background & Significance

Neonatal sepsis is associated with short and long-term complications and high mortality if untreated (1). The incidence of neonatal sepsis has been decreasing in extremely low birth weight and preterm infants, yet the incidence of neonatal sepsis associated mortality and length of hospital stay has failed to decrease (2). Rapid and accurate diagnosis based on laboratory and clinical findings remains a challenge despite extensive investigation of the molecular mechanisms behind neonatal sepsis (1). Our novel study investigates the proteome, metabolome and liquid biomarkers such as PTMs and EVs for prognostic markers of late onset sepsis using dried blood spot (DBS), comparing whole blood with plasma in a cross-species comparison.

 

Methods

DBS and plasma samples from preterm piglet experimental sepsis models and human preterm infants were used for identification of potential diagnostic and prognostic markers. Proteomics and metabolomics investigations were performed on 3 mm punched DBS samples lysed in SDS and analyzed using high-end LC-MS/MS using DIA and PASEF followed by datamining. 

 

Results and Conclusion

Recently, it has been shown that stability of proteins and metabolites in DBS samples persists and may serve as tool for diagnosis and clinical prognostics (3). Our optimized multiple-extraction strategy allowed insight into sepsis markers (>1300 proteins) and differences in whole blood vs. plasma based diagnostics.

  1. Ng S, Strunk T, Jiang P, Muk T, Sangild PT, Currie A. Precision Medicine for Neonatal Sepsis. Front Mol Biosci. 2018;5:70.
  2. Berkhout DJC, van Keulen BJ, Niemarkt HJ, Bessem JR, de Boode WP, Cossey V, et al. Late-onset Sepsis in Preterm Infants Can Be Detected Preclinically by Fecal Volatile Organic Compound Analysis: A Prospective, Multicenter Cohort Study. Clin Infect Dis [Internet]. 2018 Jun 21 [cited 2019 Apr 25];68(1):70–7. Available from: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciy383/5040327
  3. Björkesten J, Enroth S, Shen Q, Wik L, Hougaard DM, Cohen AS, et al. Stability of Proteins in Dried Blood Spot Biobanks. Mol Cell Proteomics [Internet]. 2017 [cited 2019 Jun 14];16(7):1286–96. Available from: http://www.ncbi.nlm.nih.gov/pubmed/28501802