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

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Patient recruitment and assignment.

Fig 2

Receiver operating characteristic curve for discriminating between 28-day survivors and non-survivors with sepsis in the intensive care unit using plasma segmented neutrophil-to-monocyte ratio (A), granulocyte-colony stimulating factor level (B), Interleukin-10 level (C), and monocyte human leukocyte antigen-antigen D–related expression (D). The sensitivity and specificity were determined at best cutoffs determined by Youden index.

Fig 3

Patient distributions in the training (n = 103) (A) and validation (n = 45) (B) cohort. Immune dysfunction score and 28-day mortality rate in the training (C) and validation (D) cohort.

Fig 4

Receiver operating characteristic curve for discriminating between 28-day survivors and non-survivors with sepsis in the intensive care unit of the training (n = 103) (A) and validation (n = 45) (B) cohort. (C) Kaplan-Meier survival analyses of overall survival rates of patients with high, medium, and low immune dysfunction scores in the training cohort. (n = 103) (D) Overall survival rates of patients with high, medium, and low immune score in the validation cohort. (n = 45).

Fig 5. Receiver operating characteristic curve for comparing 28-day mortality prediction performance by using different scoring system in training cohort.

Fig 6. Association between post lipopolysaccharide stimulation immune response and immune dysfunction score 0–1, 2–3, 4–5 in training cohort using Kruskal-Wallis test (n = 75).

Interleukin -6 (A), granulocyte-colony stimulating factor (B), interleukin -10 (C), and tumor necrosis factor-α (D).