Inflammatory bowel disease: is it a primary immunodeficiency?

Glocker, Erik; Grimbacher, Bodo

doi:10.1007/s00018-011-0837-9

Cited by 91 publications

(61 citation statements)

References 109 publications

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“…Moreover, it has been found that miRNAs are differentially expressed in ulcerative colitis (UC) and Crohn's disease (CD) [27] , the two main forms of IBD. However, the pathogenesis of IBD still remains enigmatic [28] , but the identification of differentially expressed miRNAs and subsequent understanding of their molecular mechanisms appear to provide new ways to reveal the pathophysiology, discover new diagnostic biomarkers, and develop new therapeutics [27] .…”

Section: Introductionmentioning

confidence: 99%

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

Coskun¹

2013

WJG

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Author contributions: Coskun M and Bjerrum JT performed the experiments and data analysis, wrote the manuscript, and wrote the final revision of the article; Troelsen JT provided with analytical tools, intellectual input and advice; Olsen J provided with reagents and human tissue; Seidelin JB and Nielsen OH contributed to the conceptual design, drafting of the manuscript and revising it critically for important intellectual content; all authors approved the final submitted manuscript. Abstract AIM: To use microarray-based miRNA profiling of colonic mucosal biopsies from patients with ulcerative colitis (UC), Crohn's disease (CD), and controls in order to identify new potential miRNA biomarkers in inflammatory bowel disease. METHODS:Colonic mucosal pinch biopsies from the descending part were obtained endoscopically from patients with active UC or CD, quiescent UC or CD, as well as healthy controls. Total RNA was isolated and miRNA expression assessed using the miRNA microarray Geniom Biochip miRNA Homo sapiens (Febit GmbH, Heidelberg, Germany). Data analysis was carried out by principal component analysis and projection to latent structure-discriminant analysis using the SIM-CA-P+12 software package (Umetrics, Umea, Sweden). The microarray data were subsequently validated by quantitative real-time polymerase chain reaction (qPCR) performed on colonic tissue samples from active UC patients (n = 20), patients with quiescent UC (n = 19), and healthy controls (n = 20). The qPCR results were analyzed with Mann-Whitney U test. In silico prediction analysis were performed to identify potential miRNA target genes and the predicted miRNA targets were then compared with all UC associated susceptibility genes reported in the literature. RESULTS:The colonic mucosal miRNA transcriptome differs significantly between UC and controls, UC and CD, as well as between UC patients with mucosal inflammation and those without. However, no clear differences in the transcriptome of patients with CD and controls were found. The miRNAs with the strongest differential power were identified (miR-20b, miR-99a, miR-203, miR-26b, and miR-98) and found to be upregulated more than a 10-fold in active UC as compared to quiescent UC, CD, and controls. Two miRNAs, miR-125b-1* and let-7e*, were up-regulated more than 5-fold in quiescent UC compared to active UC, CD, and controls. Four of the seven miRNAs (miR-20b, miR-98, miR-125b-1*, and let-7e*) were validated by qPCR and found to be specifically upregulated in patients with UC. Using in silico analysis we found several predicted pro-inflammatory target genes involved in various pathways, such as mitogen-activated protein kinase and cytokine signaling, which are both key signaling pathways in UC.

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Section: Introductionmentioning

confidence: 99%

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

Coskun¹

2013

WJG

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“…The most common autoimmune disorders in PADs are immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) [7]. Moreover, other diseases including autoimmune thyroid disease [8], type 1 diabetes (T1D) [9], rheumatoid arthritis (RA) [10], systemic lupus erythematosus (SLE) [11], dermatomyositis [12], inflammatory bowel diseases (IBD) [13], alopecia areata [11], vitiligo [8], and glomerulonephritis [14] are also common in PADs due to the lack of self-tolerance [15]. …”

Section: Introductionmentioning

confidence: 99%

Autoimmunity in Primary Antibody Deficiencies

Azizi¹,

Ahmadi²,

Abolhassani³

et al. 2016

Int Arch Allergy Immunol

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Primary antibody deficiencies (PADs) are the most common inherited primary immunodeficiencies in humans, characterized by hypogammaglobulinemia, an inability to produce specific antibodies, and recurrent infections mainly caused by encapsulated bacteria. However, it has been shown that inflammatory disorders, granulomatous lesions, lymphoproliferative diseases, cancer, and autoimmunity are associated with the various types of PAD. Both systemic and organ-specific autoimmune diseases could be attributed to B-cell defects in PAD patients. Immune thrombocytopenic purpura and autoimmune hemolytic anemia are the most common autoimmune disorders in this group of patients. The aim of this review is to describe the proposed mechanisms for autoimmunity and to review the literature with respect to the reported autoimmune disorders in each type of PAD.

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“…Pain is usually caused by abdominal cramps, owing to irritation of the nerves by inflammatory cytokines and mediators sensitizing the primary afferents and muscles controlling intestinal contractions (Bielefeldt et al, 2009;Docherty et al, 2011;Glocker and Grimbacher, 2012). Pain may be the only symptom of disease activity in some patients, and about one-sixth of IBD patients are chronically treated with opioids (Edwards et al, 2001;Cross et al, 2005;Lix et al, 2008;Bielefeldt et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Characterization of a Potent Inhibitor of Autotaxin in Animal Models of Inflammatory Bowel Disease and Multiple Sclerosis

Thirunavukkarasu

Tan

Swearingen

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Autotaxin is a secreted enzyme that catalyzes the conversion of lysophosphatidyl choline into the bioactive lipid mediator lysophosphatidic acid (LPA). It is the primary enzyme responsible for LPA production in plasma. It is upregulated in inflammatory conditions and inhibition of autotaxin may have antiinflammatory activity in a variety of inflammatory diseases. To determine the role of autotaxin and LPA in the pathophysiology of inflammatory disease states, we used a potent and orally bioavailable inhibitor of autotaxin that we have recently identified, and characterized it in mouse models of inflammation, inflammatory bowel disease (IBD), multiple sclerosis (MS), and visceral pain. Compound-1, a potent inhibitor of autotaxin with an IC 50 of ∼2 nM, has good oral pharmacokinetic properties in mice and results in a substantial inhibition of plasma LPA that correlates with drug exposure levels. Treatment with the inhibitor resulted in significant anti-inflammatory and analgesic effects in the carrageenaninduced paw inflammation and acetic acid-induced visceral pain tests, respectively. Compound-1 also significantly inhibited disease activity score in the dextran sodium sulfate-induced model of IBD, and in the experimental autoimmune encephalomyelitis model of MS. In conclusion, the present study demonstrates the anti-inflammatory and analgesic properties of a novel inhibitor of autotaxin that may serve as a therapeutic option for IBD, MS, and pain associated with inflammatory states.

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Inflammatory bowel disease: is it a primary immunodeficiency?

Cited by 91 publications

References 109 publications

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

Autoimmunity in Primary Antibody Deficiencies

Pharmacological Characterization of a Potent Inhibitor of Autotaxin in Animal Models of Inflammatory Bowel Disease and Multiple Sclerosis

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Inflammatory bowel disease: is it a primary immunodeficiency?

Cited by 91 publications

References 109 publications

miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis

Autoimmunity in Primary Antibody Deficiencies

Pharmacological Characterization of a Potent Inhibitor of Autotaxin in Animal Models of Inflammatory Bowel Disease and Multiple Sclerosis

Contact Info

Product

Resources

About

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis

miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis