Diagnosis and evaluation of severity of sepsis via the use of biomarkers and profiles of 13 cytokines: a multiplex analysis
-
Dong Wook Jekarl
, Ji Yeon Kim , Seungok Lee , Myungshin Kim , Yonggoo Kim, Kyungja Han
, Seon Hee Woo und Woon Jeong Lee
Abstract
Background: The object of this study was to evaluate biomarkers for diagnosis of sepsis, hematologic parameters, and cytokine profiles for use in the diagnosis and evaluation of severity of sepsis.
Methods: We enrolled 127 consecutive patients with systemic inflammatory response syndrome (SIRS), 97 of whom were diagnosed with sepsis. The following biomarkers were evaluated: procalcitonin (PCT); C-reactive protein (CRP); erythrocyte sedimentation rate (ESR); white blood cell count, immature granulocyte (IG) count; and multiplex cytokines, including interleukin (IL)1-β (IL1β), IL2, IL4, IL5, IL6, IL9, IL10, IL12p70, IL13, IL17, IL22, tumor necrosis factor-α (TNFα), and interferon-γ (IFNγ). A cytokine bead immunoassay was used to perform simultaneous measurements.
Results: The disease involving urinary and respiratory tract constituted 57.5% of all patients. The severity of infection was classified as follows: SIRS patients, n=30; sepsis patients, n=81; and septic shock/severe sepsis patients, n=16. PCT, IL6, and CRP had high area under receiver operation characteristic curve (AUCs) and accuracy, which is as follows: PCT: 0.841, 80.5%; IL6: 0.811, 77.1%; CRP: 0.784, 73.8%, respectively. Severity of sepsis could be discriminated by PCT, IL6, and IL5. Unlike other cytokines, IFNγ had an inverse relation with severity of sepsis. The relationship between cytokine profiles and clinical diagnosis of sepsis was unclear.
Conclusions: PCT, IL6, and CRP values could assist diagnosis, and PCT, IL6, and IL5 had discriminative properties for determination of severity of sepsis. IFNγ revealed a distinct inverse relationship with severity of sepsis. As there was no relationship between cytokine profiles and sepsis, further studies are required to develop clinical applications.
Acknowledgments
We thank Hyunyu Choi, Bumse Son, and Hyuk Kwon for excellent technical assistance. All the reagents are provided by Dong Kang Medipia, Co., Ltd., which was arranged by Dong Hwan Kim.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Financial support: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 1992;101:1644–55.10.1378/chest.101.6.1644Suche in Google Scholar PubMed
2. Marino R, Struck J, Maisel A, Magrini L, Bergmann A, Somma S. Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis. Crit Care 2014;18:1–7.10.1186/cc13731Suche in Google Scholar PubMed PubMed Central
3. Giamarellos-Bourboulis EJ, Mega A, Grecka P. Procalcitonin: a marker to clearly differentiate systemic inflammatory response syndrome and sepsis in the critically ill patient? Intensive Care Med 2002;28:1351–6.10.1007/s00134-002-1398-zSuche in Google Scholar PubMed
4. Jekarl DW, Lee SY, Lee J, Park YJ, Kim YG, Park JH, et al. Procalcitonin as a diagnostic marker and IL-6 as a prognostic marker for sepsis. Diagn Microbiol Infect Dis 2013;75:342–7.10.1016/j.diagmicrobio.2012.12.011Suche in Google Scholar PubMed
5. Ventetudo C, Levy M. Biomarkers: diagnosis and risk assessment in sepsis. Clin Chest Med 2008;29:591–603.10.1016/j.ccm.2008.07.001Suche in Google Scholar PubMed
6. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013;41:580–637.10.1097/CCM.0b013e31827e83afSuche in Google Scholar PubMed
7. Cimenti C, Erwa W, Herkner K, Kasper D, Muller W, Resch B. The predictive value of immature granulocyte count and immature myeloid information in the diagnosis of neonatal sepsis. Clin Chem Lab Med 2012;50:1429–32.10.1515/cclm-2011-0656Suche in Google Scholar PubMed
8. Park DH, Park K, Park J, Park HH, Chae H, Lim J, et al. Screening of sepsis using leukocyte cell population data from the Coulter automatic blood cell analyzer DxH800. Int J Lab Hem 2011;33:391–9.10.1111/j.1751-553X.2011.01298.xSuche in Google Scholar PubMed
9. Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau G, et al. Diagnostic value of procalcitonin, interleukin-6 and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med 2001;164:396–402.10.1164/ajrccm.164.3.2009052Suche in Google Scholar PubMed
10. Chalupa P, Beran O, Herwald H, Kasprikova N, Holub M. Evaluation of potential biomarkers for the discrimination of bacterial and viral infections. Infection 2011;39:411–7.10.1007/s15010-011-0126-4Suche in Google Scholar PubMed
11. Lvovschi V, Arnaud L, Parizot C, Freund Y, Juillien G, Ghillani-Dalbin P, et al. Cytokine profiles in sepsis have limited relevance for stratifying patients in the emergency department: a prospective observational study. PLoS One 2011;6:1–13.10.1371/journal.pone.0028870Suche in Google Scholar
12. Bozza F, Salluh J, Japiassu A, Soares M, Assis E, Gomes R, et al. Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care 2007;11:1–8.10.1186/cc5783Suche in Google Scholar
13. Mera S, Tatulescu D, Cismaru C, Bondor C, Slavcovici A, Zanc V, et al. Multiplex cytokine profiling in patients with sepsis. APMIS 2010;119:155–63.10.1111/j.1600-0463.2010.02705.xSuche in Google Scholar
14. Maenhout TM, Marcelis L. Immature granulocyte count in peripheral blood by the Sysmex haematology XN series compared to microscopic differentiation. J Clin Pathol 2014;67:648–50.10.1136/jclinpath-2014-202223Suche in Google Scholar
15. Kim MJ, Jang JW, Oh BS, Kwon JH, Chung KW, Jung HS, et al. Change in inflammatory cytokine profiles after transarterial chemotherapy in patients with hepatocellular carcinoma. Cytokine 2013;64:516–22.10.1016/j.cyto.2013.07.021Suche in Google Scholar
16. Crawley M. Multivariate analysis. In The R book. West Sussex: John Wiley & Sons, Ltd, 2007:731–47.Suche in Google Scholar
17. Angus D, Poll T. Severe sepsis and septic shock. N Engl J Med 2013;369:840–51.10.1056/NEJMra1208623Suche in Google Scholar
18. Tang B, Eslick G, Craig J, McLean A. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 2007;7:210–7.10.1016/S1473-3099(07)70052-XSuche in Google Scholar
19. Afshari A, Harbarth S. Procalcitonin as diagnostic biomarker of sepsis. Lancet Infect Dis 2013;13:382–4.10.1016/S1473-3099(13)70026-4Suche in Google Scholar
20. Moyer MW. New biomarkers sought for improving sepsis management and care. Nat Med 2013;18:999.10.1038/nm0712-999Suche in Google Scholar PubMed
21. Magrini L, Gagliano G, Travaglino F, Vetrone F, Marino R, Cardelli P, et al. Comparison between white blood cell count, procalcitonin and C reactive protein as a diagnostic and prognostic biomarkers of infection or sepsis in patients presenting to emergency department. Clin Chem Lab Med 2014;52:1465–72.10.1515/cclm-2014-0210Suche in Google Scholar PubMed
22. Boomer J, Shuherk-Shaffer J, Hotchkiss R, Green JM. A prospective analysis of lymphocyte phenotype and function over the course of acute sepsis. Crit Care 2012;16:1–14.10.1186/cc11404Suche in Google Scholar PubMed PubMed Central
Supplemental Material
The online version of this article (DOI: 10.1515/cclm-2014-0607) offers supplementary material, available to authorized users.
©2015 by De Gruyter
Artikel in diesem Heft
- Frontmatter
- Editorials
- “Personalized” sepsis care with the help of specific biomarker levels on admission and during follow up: are we there yet?
- Procalcitonin-guided antibiotic therapy: a potentially effective and efficient strategy
- Review
- The prognostic blood biomarker proadrenomedullin for outcome prediction in patients with chronic obstructive pulmonary disease (COPD): a qualitative clinical review
- General Clinical Chemistry and Laboratory Medicine
- Diagnostic testing for a high-grade inflammation: parameter dynamics and novel markers
- Serial changes in serum procalcitonin, interleukin 6, and C-reactive protein levels according to non-specific surgical stimulation
- Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia
- Presepsin as a potential marker for bacterial infection relapse in critical care patients. A preliminary study
- Diagnosis and evaluation of severity of sepsis via the use of biomarkers and profiles of 13 cytokines: a multiplex analysis
- Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a US health system perspective
- Analytical evaluation of Diazyme procalcitonin (PCT) latex-enhanced immunoturbidimetric assay on Beckman Coulter AU5800
- Calprotectin and lactoferrin in the cerebrospinal fluid; biomarkers utilisable for differential diagnostics of bacterial and aseptic meningitis?
- Cancer Diagnostics
- Increased level of circulating U2 small nuclear RNA fragments indicates metastasis in melanoma patients
- Cardiovascular Diseases
- Comparison between admission natriuretic peptides, NGAL and sST2 testing for the prediction of worsening renal function in patients with acutely decompensated heart failure
- Diabetes
- Weight loss reduces serum monocyte chemoattractant protein-1 concentrations in association with improvements in renal injury in obese men with metabolic syndrome
- Letters to the Editors
- Ranking prestige of medical and laboratory technology journals
- Expression of CD64 on neutrophils (CD64 index): diagnostic accuracy of CD64 index to predict sepsis in critically ill patients
- Measurement of apolipoprotein M in sepsis-related deaths
- The stability of select biomarkers in frozen plasma over time: an evaluation of a low-volume sample analyzer
- Is the new Beckman AccuTnI+3 assay capable of producing false-positive troponin I results?
- Spectrum of red cell abnormalities in undiagnosed hemolytic anemias and methemoglobinemias: a single center experience
- Correlation of methadone concentrations in plasma and saliva collected with and without stimulation in pain management patients
- Higher alkaline phosphatase was associated with the short-term adverse outcomes of peritoneal dialysis-related peritonitis
- The use of a rapid fluorogenic neuraminidase assay to differentiate acute Streptococcus pneumoniae-associated hemolytic uremic syndrome (HUS) from other forms of HUS
- Congress Abstracts
- 3rd EFLM-BD European Conference on Preanalytical Phase
Artikel in diesem Heft
- Frontmatter
- Editorials
- “Personalized” sepsis care with the help of specific biomarker levels on admission and during follow up: are we there yet?
- Procalcitonin-guided antibiotic therapy: a potentially effective and efficient strategy
- Review
- The prognostic blood biomarker proadrenomedullin for outcome prediction in patients with chronic obstructive pulmonary disease (COPD): a qualitative clinical review
- General Clinical Chemistry and Laboratory Medicine
- Diagnostic testing for a high-grade inflammation: parameter dynamics and novel markers
- Serial changes in serum procalcitonin, interleukin 6, and C-reactive protein levels according to non-specific surgical stimulation
- Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia
- Presepsin as a potential marker for bacterial infection relapse in critical care patients. A preliminary study
- Diagnosis and evaluation of severity of sepsis via the use of biomarkers and profiles of 13 cytokines: a multiplex analysis
- Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a US health system perspective
- Analytical evaluation of Diazyme procalcitonin (PCT) latex-enhanced immunoturbidimetric assay on Beckman Coulter AU5800
- Calprotectin and lactoferrin in the cerebrospinal fluid; biomarkers utilisable for differential diagnostics of bacterial and aseptic meningitis?
- Cancer Diagnostics
- Increased level of circulating U2 small nuclear RNA fragments indicates metastasis in melanoma patients
- Cardiovascular Diseases
- Comparison between admission natriuretic peptides, NGAL and sST2 testing for the prediction of worsening renal function in patients with acutely decompensated heart failure
- Diabetes
- Weight loss reduces serum monocyte chemoattractant protein-1 concentrations in association with improvements in renal injury in obese men with metabolic syndrome
- Letters to the Editors
- Ranking prestige of medical and laboratory technology journals
- Expression of CD64 on neutrophils (CD64 index): diagnostic accuracy of CD64 index to predict sepsis in critically ill patients
- Measurement of apolipoprotein M in sepsis-related deaths
- The stability of select biomarkers in frozen plasma over time: an evaluation of a low-volume sample analyzer
- Is the new Beckman AccuTnI+3 assay capable of producing false-positive troponin I results?
- Spectrum of red cell abnormalities in undiagnosed hemolytic anemias and methemoglobinemias: a single center experience
- Correlation of methadone concentrations in plasma and saliva collected with and without stimulation in pain management patients
- Higher alkaline phosphatase was associated with the short-term adverse outcomes of peritoneal dialysis-related peritonitis
- The use of a rapid fluorogenic neuraminidase assay to differentiate acute Streptococcus pneumoniae-associated hemolytic uremic syndrome (HUS) from other forms of HUS
- Congress Abstracts
- 3rd EFLM-BD European Conference on Preanalytical Phase