Loss of Response to Anti-Tumor Necrosis Factor Alpha Therapy in Crohn’s Disease Is Not Associated with Emergence of Novel Inflammatory Pathways

Loss of Response to Anti-Tumor Necrosis Factor Alpha Therapy in Crohn’s Disease Is Not... Background While monoclonal antibodies against tumor necrosis factor-α (TNFα) are effective in treating Crohn’s disease (CD), approximately one-third of patients lose response. The mechanisms underlying this loss of response remain elusive. Aim We sought to determine if novel biological pathways, including TNFα-independent inflammatory pathways, emerge in those with loss of response to anti-TNFα. Methods Using RNA microarray technology in 28 patients with CD, we examined the colonic gene expression differences between those with active inflammation in the setting of loss of response to TNFα-antagonist therapy (“loss of responders”) compared to anti-TNFα naïve patients with active inflammation and those on anti-TNF therapy in disease remission. Pathway enrichment analyses were performed. Results We found that colonic expression of chemokines known to drive inflammation ( CXCL20, CXCL9, and CXCL10) was elevated in those with loss of response compared to those in remission. Expression of genes critical to modulating oxidative stress burden (DUOX2, DUOXA2, and NOS2) was also elevated. Additionally, MMP3, MMP1, and MMP12 were elevated in those with continued inflammation. Gene enrichment analysis revealed that loss of responders exhibited dysregulation in the cysteine and methionine metabolism pathway, suggesting alteration in oxidative stress burden. There were no differences in genes or pathways between http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Digestive Diseases and Sciences Springer Journals

Loss of Response to Anti-Tumor Necrosis Factor Alpha Therapy in Crohn’s Disease Is Not Associated with Emergence of Novel Inflammatory Pathways

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Publisher
Springer US
Copyright
Copyright © 2018 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Medicine & Public Health; Gastroenterology; Hepatology; Oncology; Transplant Surgery; Biochemistry, general
ISSN
0163-2116
eISSN
1573-2568
D.O.I.
10.1007/s10620-018-4932-8
Publisher site
See Article on Publisher Site

Abstract

Background While monoclonal antibodies against tumor necrosis factor-α (TNFα) are effective in treating Crohn’s disease (CD), approximately one-third of patients lose response. The mechanisms underlying this loss of response remain elusive. Aim We sought to determine if novel biological pathways, including TNFα-independent inflammatory pathways, emerge in those with loss of response to anti-TNFα. Methods Using RNA microarray technology in 28 patients with CD, we examined the colonic gene expression differences between those with active inflammation in the setting of loss of response to TNFα-antagonist therapy (“loss of responders”) compared to anti-TNFα naïve patients with active inflammation and those on anti-TNF therapy in disease remission. Pathway enrichment analyses were performed. Results We found that colonic expression of chemokines known to drive inflammation ( CXCL20, CXCL9, and CXCL10) was elevated in those with loss of response compared to those in remission. Expression of genes critical to modulating oxidative stress burden (DUOX2, DUOXA2, and NOS2) was also elevated. Additionally, MMP3, MMP1, and MMP12 were elevated in those with continued inflammation. Gene enrichment analysis revealed that loss of responders exhibited dysregulation in the cysteine and methionine metabolism pathway, suggesting alteration in oxidative stress burden. There were no differences in genes or pathways between

Journal

Digestive Diseases and SciencesSpringer Journals

Published: Jan 25, 2018

References

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