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Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators

OBJECTIVES: We aimed to demonstrate the potential of precision medicine to describe the inflammatory landscape present in children with suspected appendicitis. Our primary objective was to determine levels of seven inflammatory protein mediators previously associated with intra-abdominal inflammatio...

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Autores principales: Naqvi, S. Ali, Thompson, Graham C., Joffe, Ari R., Blackwood, Jaime, Martin, Dori-Ann, Brindle, Mary, Barkema, Herman W., Jenne, Craig N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409077/
https://www.ncbi.nlm.nih.gov/pubmed/30918467
http://dx.doi.org/10.1155/2019/2359681
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author Naqvi, S. Ali
Thompson, Graham C.
Joffe, Ari R.
Blackwood, Jaime
Martin, Dori-Ann
Brindle, Mary
Barkema, Herman W.
Jenne, Craig N.
author_facet Naqvi, S. Ali
Thompson, Graham C.
Joffe, Ari R.
Blackwood, Jaime
Martin, Dori-Ann
Brindle, Mary
Barkema, Herman W.
Jenne, Craig N.
author_sort Naqvi, S. Ali
collection PubMed
description OBJECTIVES: We aimed to demonstrate the potential of precision medicine to describe the inflammatory landscape present in children with suspected appendicitis. Our primary objective was to determine levels of seven inflammatory protein mediators previously associated with intra-abdominal inflammation (C-reactive protein—CRP, procalcitonin—PCT, interleukin-6 (IL), IL-8, IL-10, monocyte chemoattractant protein-1—MCP-1, and serum amyloid A—SAA) in a cohort of children with suspected appendicitis. Subsequently, using a multiplex proteomics approach, we examined an expansive array of novel candidate cytokine and chemokines within this population. METHODS: We performed a secondary analysis of targeted proteomics data from Alberta Sepsis Network studies. Plasma mediator levels, analyzed by Luminex multiplex assays, were evaluated in children aged 5-17 years with nonappendicitis abdominal pain (NAAP), acute appendicitis (AA), and nonappendicitis sepsis (NAS). We used multivariate regression analysis to evaluate the seven target proteins, followed by decision tree and heat mapping analyses for all proteins evaluated. RESULTS: 185 children were included: 83 with NAAP, 79 AA, and 23 NAS. Plasma levels of IL-6, CRP, MCP-1, PCT, and SAA were significantly different in children with AA compared to those with NAAP (p < 0.001). Expansive proteomic analysis demonstrated 6 patterns in inflammatory mediator profiles based on severity of illness. A decision tree incorporating the proteins CRP, ferritin, SAA, regulated on activation normal T-cell expressed and secreted (RANTES), monokine induced by gamma interferon (MIG), and PCT demonstrated excellent specificity (0.920) and negative predictive value (0.882) for children with appendicitis. CONCLUSIONS: Multiplex proteomic analyses described the inflammatory landscape of children presenting to the ED with suspected appendicitis. We have demonstrated the feasibility of this approach to identify potential novel candidate cytokines/chemokine patterns associated with a specific illness (appendicitis) amongst those with a broad ED presentation (abdominal pain). This approach can be modelled for future research initiatives in pediatric emergency medicine.
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spelling pubmed-64090772019-03-27 Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators Naqvi, S. Ali Thompson, Graham C. Joffe, Ari R. Blackwood, Jaime Martin, Dori-Ann Brindle, Mary Barkema, Herman W. Jenne, Craig N. Mediators Inflamm Research Article OBJECTIVES: We aimed to demonstrate the potential of precision medicine to describe the inflammatory landscape present in children with suspected appendicitis. Our primary objective was to determine levels of seven inflammatory protein mediators previously associated with intra-abdominal inflammation (C-reactive protein—CRP, procalcitonin—PCT, interleukin-6 (IL), IL-8, IL-10, monocyte chemoattractant protein-1—MCP-1, and serum amyloid A—SAA) in a cohort of children with suspected appendicitis. Subsequently, using a multiplex proteomics approach, we examined an expansive array of novel candidate cytokine and chemokines within this population. METHODS: We performed a secondary analysis of targeted proteomics data from Alberta Sepsis Network studies. Plasma mediator levels, analyzed by Luminex multiplex assays, were evaluated in children aged 5-17 years with nonappendicitis abdominal pain (NAAP), acute appendicitis (AA), and nonappendicitis sepsis (NAS). We used multivariate regression analysis to evaluate the seven target proteins, followed by decision tree and heat mapping analyses for all proteins evaluated. RESULTS: 185 children were included: 83 with NAAP, 79 AA, and 23 NAS. Plasma levels of IL-6, CRP, MCP-1, PCT, and SAA were significantly different in children with AA compared to those with NAAP (p < 0.001). Expansive proteomic analysis demonstrated 6 patterns in inflammatory mediator profiles based on severity of illness. A decision tree incorporating the proteins CRP, ferritin, SAA, regulated on activation normal T-cell expressed and secreted (RANTES), monokine induced by gamma interferon (MIG), and PCT demonstrated excellent specificity (0.920) and negative predictive value (0.882) for children with appendicitis. CONCLUSIONS: Multiplex proteomic analyses described the inflammatory landscape of children presenting to the ED with suspected appendicitis. We have demonstrated the feasibility of this approach to identify potential novel candidate cytokines/chemokine patterns associated with a specific illness (appendicitis) amongst those with a broad ED presentation (abdominal pain). This approach can be modelled for future research initiatives in pediatric emergency medicine. Hindawi 2019-02-21 /pmc/articles/PMC6409077/ /pubmed/30918467 http://dx.doi.org/10.1155/2019/2359681 Text en Copyright © 2019 S. Ali Naqvi et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Naqvi, S. Ali
Thompson, Graham C.
Joffe, Ari R.
Blackwood, Jaime
Martin, Dori-Ann
Brindle, Mary
Barkema, Herman W.
Jenne, Craig N.
Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators
title Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators
title_full Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators
title_fullStr Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators
title_full_unstemmed Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators
title_short Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators
title_sort cytokines and chemokines in pediatric appendicitis: a multiplex analysis of inflammatory protein mediators
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409077/
https://www.ncbi.nlm.nih.gov/pubmed/30918467
http://dx.doi.org/10.1155/2019/2359681
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