Development and validation of immune dysfunction score to predict 28-day mortality of sepsis patients

PLoS One. 2017 Oct 26;12(10):e0187088. doi: 10.1371/journal.pone.0187088. eCollection 2017.

Abstract

Background: Sepsis-induced immune dysfunction ranging from cytokines storm to immunoparalysis impacts outcomes. Monitoring immune dysfunction enables better risk stratification and mortality prediction and is mandatory before widely application of immunoadjuvant therapies. We aimed to develop and validate a scoring system according to patients' immune dysfunction status for 28-day mortality prediction.

Methods: A prospective observational study from a cohort of adult sepsis patients admitted to ICU between August 2013 and June 2016 at Kaohsiung Chang Gung Memorial Hospital in Taiwan. We evaluated immune dysfunction status through measurement of baseline plasma Cytokine levels, Monocyte human leukocyte-DR expression by flow cytometry, and stimulated immune response using post LPS stimulated cytokine elevation ratio. An immune dysfunction score was created for 28-day mortality prediction and was validated.

Results: A total of 151 patients were enrolled. Data of the first consecutive 106 septic patients comprised the training cohort, and of other 45 patients comprised the validation cohort. Among the 106 patients, 21 died and 85 were still alive on day 28 after ICU admission. (mortality rate, 19.8%). Independent predictive factors revealed via multivariate logistic regression analysis included segmented neutrophil-to-monocyte ratio, granulocyte-colony stimulating factor, interleukin-10, and monocyte human leukocyte antigen-antigen D-related levels, all of which were selected to construct the score, which predicted 28-day mortality with area under the curve of 0.853 and 0.789 in the training and validation cohorts, respectively.

Conclusions: The immune dysfunction scoring system developed here included plasma granulocyte-colony stimulating factor level, interleukin-10 level, serum segmented neutrophil-to-monocyte ratio, and monocyte human leukocyte antigen-antigen D-related expression appears valid and reproducible for predicting 28-day mortality.

Publication types

  • Observational Study
  • Validation Study

MeSH terms

  • Cohort Studies
  • Cytokines / blood
  • Flow Cytometry
  • Humans
  • Lipopolysaccharides / pharmacology
  • Prospective Studies
  • Sepsis / immunology*
  • Sepsis / mortality*

Substances

  • Cytokines
  • Lipopolysaccharides

Grants and funding

The work is supported in part by grants from the Chang Gung Memorial Hospital Grant (CMRPG8B1061, CMRPG8B1062, CMRPG8B1063, CMRPG8C0551, and CMRPG8C0052 to WF Fang; CMRPG8B1071 to 73 to YH Wang; CMRPG8B1081 to 83 to CC Wang) and a grant from Taiwan Ministry of Science and Technology (MOST 104-2314-B-182A-123-) to WF Fang. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.