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Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease

AIM: To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab) level and time to surgical recurrence after initial surgery for Crohn’s disease (CD). METHODS: We reviewed 412 charts from a clinical database at tertiary academic hospita...

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Autores principales: Gathungu, Grace, Zhang, Yuanhao, Tian, Xinyu, Bonkowski, Erin, Rowehl, Leahana, Krumsiek, Julia, Nix, Billy, Chalk, Claudia, Trapnell, Bruce, Zhu, Wei, Newberry, Rodney, Denson, Lee, Li, Ellen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799863/
https://www.ncbi.nlm.nih.gov/pubmed/29434451
http://dx.doi.org/10.3748/wjg.v24.i5.623
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author Gathungu, Grace
Zhang, Yuanhao
Tian, Xinyu
Bonkowski, Erin
Rowehl, Leahana
Krumsiek, Julia
Nix, Billy
Chalk, Claudia
Trapnell, Bruce
Zhu, Wei
Newberry, Rodney
Denson, Lee
Li, Ellen
author_facet Gathungu, Grace
Zhang, Yuanhao
Tian, Xinyu
Bonkowski, Erin
Rowehl, Leahana
Krumsiek, Julia
Nix, Billy
Chalk, Claudia
Trapnell, Bruce
Zhu, Wei
Newberry, Rodney
Denson, Lee
Li, Ellen
author_sort Gathungu, Grace
collection PubMed
description AIM: To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab) level and time to surgical recurrence after initial surgery for Crohn’s disease (CD). METHODS: We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA IgG and IgA, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence. RESULTS: Ninety six percent of patients underwent initial ileocecal resection (ICR) or ileal resection (IR) and subsequently 40% of patients required a second ICR/IR for CD. GM-CSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio (HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine (HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators (HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking (HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16L1 (HR = 0.65, 95%CI: 0.49-0.88, P = 0.006). CONCLUSION: GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior.
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spelling pubmed-57998632018-02-13 Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease Gathungu, Grace Zhang, Yuanhao Tian, Xinyu Bonkowski, Erin Rowehl, Leahana Krumsiek, Julia Nix, Billy Chalk, Claudia Trapnell, Bruce Zhu, Wei Newberry, Rodney Denson, Lee Li, Ellen World J Gastroenterol Retrospective Study AIM: To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab) level and time to surgical recurrence after initial surgery for Crohn’s disease (CD). METHODS: We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA IgG and IgA, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence. RESULTS: Ninety six percent of patients underwent initial ileocecal resection (ICR) or ileal resection (IR) and subsequently 40% of patients required a second ICR/IR for CD. GM-CSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio (HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine (HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators (HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking (HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16L1 (HR = 0.65, 95%CI: 0.49-0.88, P = 0.006). CONCLUSION: GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior. Baishideng Publishing Group Inc 2018-02-07 2018-02-07 /pmc/articles/PMC5799863/ /pubmed/29434451 http://dx.doi.org/10.3748/wjg.v24.i5.623 Text en ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
spellingShingle Retrospective Study
Gathungu, Grace
Zhang, Yuanhao
Tian, Xinyu
Bonkowski, Erin
Rowehl, Leahana
Krumsiek, Julia
Nix, Billy
Chalk, Claudia
Trapnell, Bruce
Zhu, Wei
Newberry, Rodney
Denson, Lee
Li, Ellen
Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease
title Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease
title_full Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease
title_fullStr Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease
title_full_unstemmed Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease
title_short Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal Crohn’s disease
title_sort impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal crohn’s disease
topic Retrospective Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799863/
https://www.ncbi.nlm.nih.gov/pubmed/29434451
http://dx.doi.org/10.3748/wjg.v24.i5.623
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