Molecular Classification of Crohn's Disease and Ulcerative Colitis Patients Using Transcriptional Profiles in Peripheral Blood Mononuclear Cells
Journal of Molecular DiagnosticsPublished 1 February 2006Open access
Michael E. Burczynski, Ron Peterson, Natalie C. Twine, Krystyna Zuberek, Brendan J. Brodeur, Lori Casciotti
Citations243
SJR quartileQ1
SJR score1.29
SNIP0.99
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The results suggest that a peripheral blood mononuclear cell-based gene expression signature can provide a molecular biomarker that can complement the standard diagnosis of UC and CD.
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) are common inflammatory bowel diseases producing intestinal inflammation and tissue damage. Although emerging evidence suggests these diseases are distinct, approximately 10% of patients remain classified as indeterminate inflammatory bowel disease even after invasive colonoscopy intended for diagnosis. A molecular diagnostic assay using a clinically accessible tissue would greatly assist in the classification of these diseases. In the present study we assessed transcriptional profiles in peripheral blood mononuclear cells from 42 healthy individuals, 59 CD patients, and 26 UC patients by hybridization to microarrays interrogating more than 22,000 sequences. Supervised analysis identified a set of 12 genes that distinguished UC and CD patient samples with high accuracy. The alterations in transcript levels observed by microarray were verified by real-time polymerase chain reaction. The results suggest that a peripheral blood mononuclear cell-based gene expression signature can provide a molecular biomarker that can complement the standard diagnosis of UC and CD.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
ScienceMolecular Classification of Cancer: Class Discovery and Class Prediction by Gene Expression Monitoring
11,622 Citations1999Todd R. Golub, Donna K. Slonim +10 more
A generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case and suggests a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge.
Nature reviews. ImmunologyThe immunological and genetic basis of inflammatory bowel disease
1,778 Citations2003Gerd Bouma, Warren Strober
The most important finding is the identification of mutations in the gene that encodes NOD2 (nucleotide-binding oligomerization domain 2) protein in a subgroup of patients with Crohn's disease.
PubMedActivated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients.
872 Citations2001Jan Schmielau, Olivera J. Finn
It is shown that freshly obtained granulocytes from healthy donors, if activated, can also inhibit cytokine production by T cells, and that granulocyte-derived H( 2)O(2) is the major cause of severe systemic T-cell suppression.
Human Molecular GeneticsUlcerative colitis and Crohn's disease: distinctive gene expression profiles and novel susceptibility candidate genes
385 Citations2001Ian C. Lawrance
Overall, significant differences in the expression profiles of 170 genes identified UC andCD as distinct molecular entities and the genomic map locations of the dysregulated genes may identify novel candidates for UC and CD genetic susceptibility.
BloodTranscript profiling of human platelets using microarray and serial analysis of gene expression
368 Citations2003Dmitri V. Gnatenko, John J. Dunn +4 more
The American Journal of GastroenterologyPlatelets in Inflammatory Bowel Disease: Clinical, Pathogenic, and Therapeutic Implications
247 Citations2004Silvio Danese, Carol de la Motte +1 more
The aim of this article is to review data on the existence of platelet dysfunction in IBD, substantiate platelets' inflammatory potential, discuss the implications of abnormal platelet activity for chronic intestinal inflammation, and consider the potential benefits of Platelet modulation for treatment of IBD.
The LancetUlcerative colitis
234 Citations2002Richard J. Farrell, Mark A. Peppercorn
Probiotics seem the most promising of several experimental and traditional agents that have been investigated in controlled clinical trials that have the potential to help treat ulcerative colitis.
The Journal of ImmunologyCutting Edge: Molecular Portrait of Human Autoimmune Disease
204 Citations2002Kevin Maas, Sanny K. Chan +5 more
To their surprise, genes with a distinct expression pattern in autoimmunity are not necessarily “immune response” genes, but are genes that encode proteins involved in apoptosis, cell cycle progression, cell differentiation, and cell migration.
Journal of Clinical PathologyIndeterminate colitis
202 Citations2004Maha Guindi, Robert H. Riddell
The role of ancillary tests in the distinction of UC from CD is reviewed and some personal observations and viewpoints are offered, and an approach to some of the relatively more esoteric combinations of findings are proposed.
Journal of Clinical PathologyHow could pathologists improve the initial diagnosis of colitis? Evidence from an international workshop
158 Citations2002Edward Bentley, D Jenkins +2 more
A full colonoscopic series gave more accurate diagnosis than a rectal biopsy, and accurate pathologists used the same evidence based criteria for multiple biopsies as for single biopsy.
PubMedDisease-associated expression profiles in peripheral blood mononuclear cells from patients with advanced renal cell carcinoma.
152 Citations2003Natalie C. Twine, Jennifer A. Stover +11 more
This work identified transcripts expressed differentially between PBMCs from renal cell carcinoma patients and normal subjects, some of which appear to reflect specific immune responses of circulating cells.
Genome biologyEvaluation of normalization procedures for oligonucleotide array data based on spiked cRNA controls
121 Citations2001Andrew A. Hill, Eugene L. Brown +4 more
The scaled-frequency method enables the comparison of expression measurements across different array designs, yields estimates of absolute message abundance in cRNA and determines the sensitivity of individual arrays, a convenient, reproducible technique that performs as well as global normalization on serial experiments with the same array design, while offering several additional features.
GutDisturbed fibrinolysis in patients with inflammatory bowel disease. A study in blood plasma, colon mucosa, and faeces.
104 Citations1989E.M.G.J. de Jong, Robert J. Porte +3 more
Patients with inflammatory bowel disease have significant changes in components of the fibrinolytic and coagulation system both systemically and locally in colon mucosa that might contribute to an increased risk for thromboembolic complications and possibly to the pathogenesis of the colitis and to the local complications such as bleeding.
GutSystemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn’s disease differentially activate the innate immune response
88 Citations2003Elizabeth Furrie, S Macfarlane +2 more
Changes in mucosal bacteria, and a switch from internal to surface antigen/antibody reactivity of a predominantly IgG1 type, leads to greater opsonisation of the respiratory burst in PMN, providing a mechanism for maintaining the inflammatory state in UC.
Toxicology and Applied PharmacologySurrogate tissue analysis: monitoring toxicant exposure and health status of inaccessible tissues through the analysis of accessible tissues and cells
81 Citations2003John C Rockett, Michael E. Burczynski +4 more
A discussion of STA based on presentations given at the Society of Toxicology's 2003 annual meeting's "Innovations in Applied Toxicology" symposium" discusses various potential applications and some of the challenges that must be overcome if this concept is to be proven.
GutLocal IgA subclass alterations in ulcerative colitis and Crohn's disease of the colon.
55 Citations1987K Kett, P Brandtzæg
There is an influx and/or proliferation of B cells representing systemic secondary immunity in the lesions of both diseases, and the mucosal shift towards IgA 1 production paralleled the magnitude of the submucosal IgA1 cell proportion in individual tissue samples.
Thrombosis and HaemostasisPlasminogen Activators in the Intestine of Patients with Inflammatory Bowel Disease
33 Citations1988P.A.F. de Bruin, G Crama-Bohbouth +5 more
Plasminogen activators determined in intestinal tissue, obtained after surgery from patients with Crohn’s disease and ulcerative colitis, and compared with normal intestinal tissue from colorectal cancer patients found to decrease with the severity of inflammation in the patients with inflammatory bowel disease.
Clinical NutritionPeripheral blood mononuclear cell fatty acid composition and inflammatory mediator production in adult Crohn's disease
32 Citations2004Timothy M Trebble, Nigel Arden +6 more
CD is associated with a greater availability, and not a deficiency, of n-3 PUFA in PBMC, but lower concentrations of AA, and lower rates of production of PGE2 and IFN-gamma, compared to healthy controls.
GutRelated IgA1 and IgG producing cells in blood and diseased mucosa in ulcerative colitis
31 Citations2002Vinay Thoree, S J C Golby +5 more
The clonal distribution and characteristics of IgG and related IgA in the mucosa and blood of patients with UC suggest a peripheral response is expressed and expanded in the colonic mucosa, and it is shown that JH1 usage was characteristic of the peripheral repertoire.
Clinical ImmunologyGene expression in mononuclear cells from patients with inflammatory bowel disease
30 Citations2004Elizabeth E. Mannick, Joseph C. Bonomolo +10 more
Examination of changes in gene expression in peripheral blood mononuclear cells in patients with untreated Crohn's disease and ulcerative colitis found genes regulating hematopoietic cell differentiation and leukemogenesis, lipid raft-associated signaling, the actin cytoskeleton, and vesicular trafficking differentially expressed.
PubMedImmunoglobulins and IgG subclasses in patients with inflammatory bowel disease.
28 Citations1999Ioanna Gouni‐Berthold, B Baumeister +2 more
Some of the IgG immunoglobulin subclass concentration changes correlate, positively or negatively, with disease activity and therefore could be used as additional markers of it in IBD, however, serum immunoglobeulin levels cannot be used to differentiate between UC and CD.
Inflammatory Bowel DiseasesApplication of Genome-Wide Gene Expression Profiling by High-Density DNA Arrays to the Treatment and Study of Inflammatory Bowel Disease
27 Citations2002Elaine E. Warner, Brian K. Dieckgraefe
Journal of Cellular PhysiologyRegulation by prostaglandin E2 of interleukin release by T lymphocytes in mucosa
21 Citations1996Susan Barrera, Joyce Lai +2 more
It is concluded that prostaglandin E2 in nM concentrations is an important modulator of cytokine release from T lymphocytes derived from the gastrointestinal tract, and it may play a central role in regulation of lamina propria immunocyte populations residing there.
Drugs of todayInflammatory bowel disease (ulcerative colitis and Crohn'sdisease): Diagnostic criteria and differential diagnosis
16 Citations1998Katrine Winther
The inflammatory bowel diseases, ulcerative colitis and Crohn's disease, continue to be etiological and diagnostic challenges and increased use of standardized criteria and diagnostic algorithms are essential instruments to improve the overall quality of the management of patients with these diseases.
PubMedAlteration of prostaglandin E2 and leukotriene B4 synthesis in chronic inflammatory bowel disease.
15 Citations1997Christian Schmidt, B Baumeister +3 more
It is concluded that prostaglandin E2, compared to leukotriene B4, is the dominant eicosanoid in moderate inflammatory bowel disease.
GutBiased J <sub>H</sub> usage in plasma cell immunoglobulin gene sequences from colonic mucosa in ulcerative colitis but not in Crohn’s disease
10 Citations1999Deborah K. Dunn‐Walters, Laurent Boursier +2 more
There is a fundamental difference in the immunoglobulin genes from patients with ulcerative colitis, and an increase in the use of JH6 and DXP′1, and a decrease in theUse ofJH4, gene segments in Immunoglobulins from lamina propria plasma cells, and from virgin IgD+ B cells, were found in patients with Ulcerative Colitis.