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Development and validation of a novel sepsis biomarker based on amino acid profiling

 Sunyoung Ahn  ;  Su Hwan Lee  ;  Kyung Soo Chung  ;  Nam Su Ku  ;  Young-Min Hyun  ;  Sail Chun  ;  Moo Suk Park  ;  Sang-Guk Lee 
 CLINICAL NUTRITION, Vol.40(6) : 3668-3676, 2021-06 
Journal Title
Issue Date
Amino acids ; Biomarker ; Kynurenine ; Mass-spectrometry ; Metabolomics ; Sepsis
Background & aims: Sepsis is a potentially fatal condition influenced by pathogens and host factors. Current sepsis biomarkers such as white blood cell count and C-reactive protein and procalcitonin levels show unsatisfactory performance in terms of diagnostic sensitivity and specificity in clinical practice. Thus, we developed and validated a new sepsis biomarker based on amino acid profiling.

Methods: We used two independent groups. The training and validation groups included 161 and 22 healthy controls, 123 and 50 patients with systemic inflammatory response syndrome, and 115 and 45 patients with sepsis, respectively. Using mass spectrometry, we measured and analyzed serum amino acid levels to select candidate amino acids that could differentiate sepsis from other conditions. Then, several possible multivariate indexes were developed by generating formulae with different combinations of candidate amino acids. The formula showing the best performance was selected and validated further.

Results: Kynurenine, tryptophan, phenylalanine, arginine, aspartic acid, glutamic acid, and glutamine were selected as candidate amino acids. Ten possible formulae were generated, and the formula with the highest diagnostic performance, which included kynurenine, tryptophan, phenylalanine, and arginine, was selected. In the validation group, the area under the receiving operating characteristic curve of the selected multivariate index (0.931) was similar to that of procalcitonin (0.945). Moreover, the generated multivariate index showed potential as a prognostic marker.

Conclusions: Serum amino acid composition in patients with sepsis differs significantly from that in healthy individuals and patients with inflammation only. The newly developed multivariate index is expected to be implementable as a sepsis biomarker in clinical practice in the near future.
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1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Ku, Nam Su(구남수) ORCID logo https://orcid.org/0000-0002-9717-4327
Park, Moo Suk(박무석) ORCID logo https://orcid.org/0000-0003-0820-7615
Lee, Sang-Guk(이상국) ORCID logo https://orcid.org/0000-0003-3862-3660
Lee, Su Hwan(이수환) ORCID logo https://orcid.org/0000-0002-3487-2574
Jung, Kyung Soo(정경수) ORCID logo https://orcid.org/0000-0003-1604-8730
Hyun, Young-Min(현영민) ORCID logo https://orcid.org/0000-0002-0567-2039
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