Defective acute inflammation in Crohn's disease: a clinical investigation

@article{Marks2006DefectiveAI,
  title={Defective acute inflammation in Crohn's disease: a clinical investigation},
  author={Daniel Marks and Marcus Wn Harbord and Raymond J Macallister and Farooq Z Rahman and Jodi Young and Bissan Al-Lazikani and William D. Lees and Marco Novelli and Stuart L Bloom and Anthony Walter Segal},
  journal={The Lancet},
  year={2006},
  volume={367},
  pages={668-678}
}
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400 Citations
Highly Influential Citations
10
Background Citations
116
Methods Citations
8
Results Citations
13

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400 Citations

Crohn’s disease is caused by a failure of the innate immune response with major abnormalities in macrophage biology
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  • Medicine
    Journal of Translational Medicine
  • 2010
TLDR
These studies demonstrated that Crohn’s patients possess a constitutionally weak innate immune response that leads to impaired removal of intestinal contents that breach the mucosal barrier of the bowel wall, resulting in granuloma formation and chronic inflammation.
An investigation of molecular defects underlying impaired acute inflammation in Crohn’s disease
TLDR
A role for immune deficiency in the pathogenesis of CD is supported and abnormal optineurin expression is identified as a relevant molecular abnormality in a subset of patients.
Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is associated with reduced optineurin expression in a subset of patients
TLDR
Identifying and studying subgroups of patients with shared defective gene expression could aid the understanding of the mechanisms underlying highly heterogeneous diseases such as Crohn's disease.
Defective innate immunity in inflammatory bowel disease: a Crohn's disease exclusivity?
  • D. Marks
  • Medicine, Biology
    Current opinion in gastroenterology
  • 2011
TLDR
The demonstration of impaired acute inflammation in Crohn's disease provides a novel mechanism for its pathogenesis, with diminished macrophage cytokine production and neutrophil recruitment leading to reduced bacterial clearance.
LPS-Stimulated Whole Blood Cytokine Production Is Not Related to Disease Behavior in Patients with Quiescent Crohn's Disease
TLDR
It is suggested that genetically determined levels of these cytokines obtained from LPS-stimulated whole blood cultures are not linked with disease behavior or severity.
Studies on patients establish Crohn's disease as a manifestation of impaired innate immunity
  • A. Segal
  • Medicine, Biology
    Journal of internal medicine
  • 2019
TLDR
Evidence is provided, obtained from patients with this condition, that the common predisposition to Crohn's is a failure of the acute inflammatory response to tissue damage, which leads to a chronic granulomatous inflammation.
What Is Wrong with Granulocytes in Inflammatory Bowel Diseases?
TLDR
Stimulation of the innate immune system in CD, particularly in patients in remission, may be an alternative therapeutic strategy that could reduce the risk of future disease relapses.
Innate immunity in inflammatory bowel disease: a disease hypothesis
TLDR
Rather than Crohn's disease being caused by excessive inflammation, the primary mechanism is actually that of an immunodeficiency, which can be compensated in some circumstances by signalling through NOD2.
Defective IL‐10 production in severe phenotypes of Crohn's disease
TLDR
A defect in IL‐10 production is shown in whole blood cell cultures and MDDCs in patients with severe forms of Crohn's disease, which may represent a mechanism mediating more severe manifestations of the disease.
Peripheral Monocyte Functions and Activation in Patients with Quiescent Crohn’s Disease
TLDR
It is highlighted that defective innate immune mechanisms in CD seems to play a role in the (inflamed) intestinal mucosa rather than in peripheral blood, and peripheral blood monocytes from CD patients in clinical remission were not impaired compared to healthy controls.
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