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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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/2359681 |
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| author | S. Ali Naqvi Graham C. Thompson Ari R. Joffe Jaime Blackwood Dori-Ann Martin Mary Brindle Herman W. Barkema Craig N. Jenne |
| author_facet | S. Ali Naqvi Graham C. Thompson Ari R. Joffe Jaime Blackwood Dori-Ann Martin Mary Brindle Herman W. Barkema Craig N. Jenne |
| author_sort | S. Ali Naqvi |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-4627470b1b774ae1965d9c1831874dde |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-4627470b1b774ae1965d9c1831874dde2025-02-03T01:00:01ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/23596812359681Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein MediatorsS. Ali Naqvi0Graham C. Thompson1Ari R. Joffe2Jaime Blackwood3Dori-Ann Martin4Mary Brindle5Herman W. Barkema6Craig N. Jenne7Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary AB, CanadaDepartment of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary AB, CanadaDepartment of Pediatrics, Division of Critical Care, University of Alberta, Edmonton AB, CanadaDepartment of Pediatrics, Division of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary AB, CanadaDepartment of Pediatrics, Division of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary AB, CanadaDepartment of Surgery, Cumming School of Medicine, University of Calgary, Calgary AB, CanadaDepartment of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary AB, CanadaDepartment of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary AB, CanadaObjectives. 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.http://dx.doi.org/10.1155/2019/2359681 |
| spellingShingle | S. Ali Naqvi Graham C. Thompson Ari R. Joffe Jaime Blackwood Dori-Ann Martin Mary Brindle Herman W. Barkema Craig N. Jenne Cytokines and Chemokines in Pediatric Appendicitis: A Multiplex Analysis of Inflammatory Protein Mediators Mediators of Inflammation |
| 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 |
| url | http://dx.doi.org/10.1155/2019/2359681 |
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