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Increased PD-1 Expression and Altered T Cell Repertoire Diversity Predict Mortality in Patients with Septic Shock: A Preliminary Study.

ABSTRACT: Sepsis causes impairment of innate and adaptive immunity by multiple mechanisms, including depletion of immune effector cells and T cell exhaustion. Although lymphocyte dysfunction is associated with increased mortality and potential reactivation of latent viral infection in patients with septic shock, the relation between viral reactivation and lymphocyte dysfunction is obscure. The objectives of this study were 1) to determine the relation of lymphocyte dysfunction to viral reactivation and mortality, and 2) to evaluate recovery of lymphocyte function during septic shock, including T cell receptor (TCR) diversity and the expression of programmed death 1 (PD-1). In 18 patients with septic shock and latent cytomegalovirus (CMV) infection, serial blood samples were obtained on days 1, 3, and 7 after the onset of shock, and immune cell subsets and receptor expression were characterized by flow cytometry. TCR diversity of peripheral blood mononuclear cells was analyzed by Multi-N-plex PCR, and CMV DNA was quantified using a real-time PCR kit. A decrease of TCR diversity and monocyte HLA-DR expression were observed in the early stage of septic shock, while CD4+ T cells displayed an increase of PD-1 expression. Significant lymphopenia persisted for at least 7 days following the onset of septic shock. Normalization of TCR diversity and PD-1 expression was observed by day 7, except in patients who died. CMV reactivation was detected in 3 of the 18 patients during the first week of their ICU stay and all 3 patients died. These changes are consistent with the early stage of immune cell exhaustion and indicate the importance of normal lymphocyte function for recovery from septic shock. Ongoing lymphocyte dysfunction is associated with CMV reactivation and dissemination, as well as with unfavorable outcomes.

SUBMITTER: Tomino A

PROVIDER: S-EPMC5225000 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Increased PD-1 Expression and Altered T Cell Repertoire Diversity Predict Mortality in Patients with Septic Shock: A Preliminary Study.

Tomino Atsutoshi A Tsuda Masanobu M Aoki Ruri R Kajita Yuka Y Hashiba Masamitsu M Terajima Tsuguaki T Kano Hideki H Takeyama Naoshi N

PloS one 20170110 1

Sepsis causes impairment of innate and adaptive immunity by multiple mechanisms, including depletion of immune effector cells and T cell exhaustion. Although lymphocyte dysfunction is associated with increased mortality and potential reactivation of latent viral infection in patients with septic shock, the relation between viral reactivation and lymphocyte dysfunction is obscure. The objectives of this study were 1) to determine the relation of lymphocyte dysfunction to viral reactivation and mo ...[more]

PMID: 28072859

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Project description:BACKGROUND:Assessment of disease severity in patients with septic shock (SS) is crucial in determining optimal level of care. In both pre- and in-hospital settings, the clinical picture alone is not sufficient for assessing disease severity and outcomes. Because blood lactate level is included in the clinical criteria of SS it should be considered to improve the assessment of its severity. This study aims to investigate the relationship between pre-hospital blood lactate level and 30-day mortality in patients with SS. METHODS:From 15 April 2017 to 15 April 2019, patients with SS requiring pre-hospital Mobile Intensive Care Unit intervention (MICU) were prospectively included in the LAPHSUS study, an observational, non-randomized controlled study. Pre-hospital blood lactate levels were measured at the time of first contact between the patients and the MICU. RESULTS:Among the 183 patients with septic shock requiring action by the MICU drawn at random from LAPHSUS study patients, six (3%) were lost to follow-up on the 30th day and thus 177 (97%) were analyzed for blood lactate levels (mean age 70 ± 14 years). Pulmonary, urinary and digestive infections were probably the cause of the SS in respectively 58%, 21% and 11% of the cases. The 30-day overall mortality was 32%. Mean pre-hospital lactatemia was significantly different between patients who died and those who survived (respectively 7.1 ± 4.0 mmol/L vs. 5.9 ± 3.5 mmol/L, p < 10-3). Using Cox regression analysis adjusted for potential confounders we showed that a pre-hospital blood lactate level ? 4 mmol/L significantly predicted 30-day mortality in patients with SS (adjusted hazard ratio = 2.37, 95%CI (1.01-5.57), p = 0.04). CONCLUSION:In this study, we showed that pre-hospital lactatemia predicts 30-day mortality in patients with septic shock handled by the MICU. Further studies will be needed to evaluate if pre-hospital lactatemia alone or combined with clinical scores could affect the triage decision-making process for those patients.

Project description:BackgroundPatients with septic shock have the highest risk of death from sepsis, however, racial disparities in mortality outcomes in this cohort have not been rigorously investigated. Our objective was to describe the association between race/ethnicity and mortality in patients with septic shock.MethodsOur study is a retrospective cohort study of adult patients in the OneFlorida Data Trust (Florida, United States of America) admitted with septic shock between January 2012 and July 2018. We identified patients as having septic shock if they received vasopressors during their hospital encounter and had either an explicit International Classification of Disease (ICD) code for sepsis, or had an infection ICD code and received intravenous antibiotics. Our primary outcome was 90-day mortality. Our secondary outcome was in-hospital mortality. Multiple logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) for variable selection was used to assess associations.FindingsThere were 13,932 patients with septic shock in our cohort. The mean age was 61 years (SD 16), 68% of the cohort identified as White (n = 9419), 28% identified as Black (n = 3936), 2% (n = 294) identified as Hispanic ethnicity, and 2% as other races not specified in the previous groups (n = 283). In our logistic regression model for 90-day mortality, patients identified as Black had 1.57 times the odds of mortality (95% CI 1.07-2.29, p = 0.02) compared to White patients. Other significant predictors included mechanical ventilation (OR 3.66, 95% CI 3.35-4.00, p < 0.01), liver disease (OR 1.75, 95% CI 1.59-1.93, p < 0.01), laboratory components of the Sequential Organ Failure Assessment score (OR 1.18, 95% CI 1.16-1.21, p < 0.01), lactate (OR 1.10, 95% CI 1.08-1.12, p < 0.01), congestive heart failure (OR 1.19, 95% CI 1.10-1.30, p < 0.01), human immunodeficiency virus (OR 1.35, 95% CI 1.04-1.75, p = 0.03), age (OR 1.04, 95% CI 1.04-1.04, p < 0.01), and the interaction between age and race (OR 0.99, 95% CI 0.99-1.00, p < 0.01). Among younger patients (<45 years), patients identified as Black accounted for a higher proportion of the deaths. Results were similar in the in-hospital mortality model.InterpretationIn this retrospective study of septic shock patients, we found that patients identified as Black had higher odds of mortality compared to patients identified as non-Hispanic White. Our findings suggest that the greatest disparities in mortality are among younger Black patients with septic shock.FundingNational Institutes of Health National Center for Advancing Translational Sciences (1KL2TR001429); National Institute of Health National Institute of General Medical Sciences (1K23GM144802).

Dataset Information

Increased PD-1 Expression and Altered T Cell Repertoire Diversity Predict Mortality in Patients with Septic Shock: A Preliminary Study.

Publications

Increased PD-1 Expression and Altered T Cell Repertoire Diversity Predict Mortality in Patients with Septic Shock: A Preliminary Study.

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