PMID- 28419100
OWN - NLM
STAT- MEDLINE
DCOM- 20170522
LR  - 20170522
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 4
DP  - 2017
TI  - Validation of two multiplex platforms to quantify circulating markers of
      inflammation and endothelial injury in severe infection.
PG  - e0175130
LID - 10.1371/journal.pone.0175130 [doi]
AB  - Biomarkers can prognosticate outcome and enable risk-stratification. In severe
      infection, focusing on multiple markers reflecting pathophysiological mechanisms 
      of organ injury could enhance management and pathway-directed therapeutics.
      Limited data exist on the performance of multiplex biomarker platforms. Our goal 
      was to compare endothelial and immune activation biomarkers in severe pediatric
      infections using two multiplex platforms. Frozen plasma from 410 children
      presenting to the Jinja Regional Hospital in Uganda with suspected infection was 
      used to measure biomarkers of endothelial (Angiopoietin-2, sFlt-1, sVCAM-1,
      sICAM-1) and immune (IL-6, IP-10, sTNFR-1, CHI3L1) activation. Two multiplex
      platforms (Luminex(R), EllaTM) based on monoclonal antibody sandwich immunoassays
      using biotin-streptavidin conjugate chemistry were selected with reagents from
      R&D Systems. The two platforms differed in ease and time of completion, number of
      samples per assay, and dynamic concentration range. Intra-assay variability
      assessed using a coefficient of variation (CV%) was 2.2-3.4 for Luminex(R) and
      1.2-2.9 for EllaTM. Correlations for biomarker concentrations within dynamic
      range of both platforms were best for IL-6 (rho = 0.96, p<0.0001), IP-10 (rho =
      0.94, p<0.0001) and sFlt-1 (rho = 0.94, p<0.0001). Agreement between
      concentrations obtained by both methods assessed by the Bland-Altman test varied,
      with best agreement for CHI3L1. Our data suggest that biomarkers of endothelial
      and immune activation can be readily measured with multiplex platforms.
      Luminex(R) and EllaTM produced reliable results with excellent CV% values. The
      EllaTM platform was more automated and completed in 75 minutes, potentially
      compatible with near-patient use. Trends in concentrations obtained by these
      methods were highly correlated, although absolute values varied, suggesting
      caution is required when comparing data from different multiplex platforms.
FAU - Leligdowicz, Aleksandra
AU  - Leligdowicz A
AUID- ORCID: http://orcid.org/0000-0001-6055-4644
AD  - Department of Medicine, University of Toronto, Toronto, Canada.
AD  - Sandra A. Rotman Laboratories, Sandra Rotman Centre for Global Health, University
      Health Network, Toronto, Canada.
FAU - Conroy, Andrea L
AU  - Conroy AL
AD  - Department of Pediatrics, Indiana University School of Medicine, Indianapolis,
      United States of America.
FAU - Hawkes, Michael
AU  - Hawkes M
AD  - Division of Pediatric Infectious Diseases, University of Alberta, Edmonton,
      Canada.
FAU - Zhong, Kathleen
AU  - Zhong K
AD  - Department of Medicine, University of Toronto, Toronto, Canada.
FAU - Lebovic, Gerald
AU  - Lebovic G
AD  - Applied Health Research Centre, The HUB, Li Ka Shing Knowledge Institute,
      University of Toronto, Toronto, Canada.
FAU - Matthay, Michael A
AU  - Matthay MA
AD  - Departments of Medicine and Anesthesia, University of California, San Francisco, 
      United States of America.
AD  - Cardiovascular Research Institute, University of California, San Francisco,
      United States of America.
FAU - Kain, Kevin C
AU  - Kain KC
AD  - Department of Medicine, University of Toronto, Toronto, Canada.
AD  - Sandra A. Rotman Laboratories, Sandra Rotman Centre for Global Health, University
      Health Network, Toronto, Canada.
LA  - eng
PT  - Journal Article
PT  - Validation Studies
DEP - 20170418
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Angiopoietin-2)
RN  - 0 (Biomarkers)
RN  - 0 (CHI3L1 protein, human)
RN  - 0 (CXCL10 protein, human)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Chitinase-3-Like Protein 1)
RN  - 0 (Interleukin-6)
RN  - 0 (Reagent Kits, Diagnostic)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 2.7.10.1 (FLT1 protein, human)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
SB  - IM
MH  - Angiopoietin-2/blood
MH  - Biomarkers/*blood
MH  - Chemokine CXCL10/blood
MH  - Child, Preschool
MH  - Chitinase-3-Like Protein 1/blood
MH  - Cohort Studies
MH  - Endothelium, Vascular/*metabolism/pathology
MH  - Humans
MH  - Immunoassay/*methods
MH  - Infant
MH  - Infection/*complications
MH  - Inflammation/*blood/complications/diagnosis
MH  - Intercellular Adhesion Molecule-1/blood
MH  - Interleukin-6/blood
MH  - Reagent Kits, Diagnostic/standards
MH  - Receptors, Tumor Necrosis Factor, Type I/blood
MH  - Reproducibility of Results
MH  - Sensitivity and Specificity
MH  - Severity of Illness Index
MH  - Vascular Cell Adhesion Molecule-1/blood
MH  - Vascular Endothelial Growth Factor Receptor-1/blood
PMC - PMC5395141
EDAT- 2017/04/19 06:00
MHDA- 2017/05/23 06:00
CRDT- 2017/04/19 06:00
PHST- 2016/11/30 00:00 [received]
PHST- 2017/03/21 00:00 [accepted]
PHST- 2017/04/19 06:00 [entrez]
PHST- 2017/04/19 06:00 [pubmed]
PHST- 2017/05/23 06:00 [medline]
AID - 10.1371/journal.pone.0175130 [doi]
AID - PONE-D-16-47489 [pii]
PST - epublish
SO  - PLoS One. 2017 Apr 18;12(4):e0175130. doi: 10.1371/journal.pone.0175130.
      eCollection 2017.