Correlation of Biomarker Expression in Colonic Mucosa with Disease Phenotype in Crohn’s Disease and Ulcerative Colitis

Abstract

Background Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by chronic intestinal inflammation due to immunological, microbial and environmental factors in genetically predisposed individuals. Advances in the diagnosis, prognosis and treatment of IBD require the identification of robust biomarkers that can be used for molecular classification of diverse disease presentations. We previously identified five genes, RELA, TNFAIP3 (A20), PIGR, TNF and IL8, whose mRNA levels in colonic mucosal biopsies could be used in a multivariate analysis to classify patients with Crohn’s disease (CD) based on disease behavior and responses to therapy. Aim We compared expression of these 5 biomarkers in IBD patients classified as having CD or ulcerative colitis (UC), and in healthy controls. Results Patients with CD were characterized as having decreased median expression of TNFAIP3, PIGR and TNF in non-inflamed colonic mucosa as compared to healthy controls. By contrast, UC patients exhibited decreased expression of PIGR and elevated expression of IL8 in colonic mucosa compared to healthy controls. A multivariate analysis combining mRNA levels for all 5 genes resulted in segregation of individuals based on disease presentation (CD vs. UC) as well as severity, i.e., patients in remission vs. those with acute colitis at the time of biopsy. Conclusion We propose that this approach could be used as a model for molecular classification of IBD patients, which could further be enhanced by the inclusion of additional genes that are identified by functional studies, global gene expression analyses, and genome-wide association studies.

The Role of the Polymeric Immunoglobulin Receptor and Secretory Immunoglobulins during Mucosal Infection and Immunity

“…PIgR KO mice have enhanced ileal IFNγ and iNOS levels compared to controls [ 53 ], likely because of the increases in certain immune cell subsets. Given alterations in antigen-presenting cells and inflammatory mediators in pIgR KO mice, it is hardly surprising then, that inflammatory diseases such as chronic obstructive pulmonary disease [ 55 , 60 , 61 , 62 ], DSS-induced and T-cell-mediated colitis in mice [ 58 , 63 ], as well as Crohn’s disease and ulcerative colitis in humans [ 64 , 65 ] are highly prevalent when SIgs are absent or reduced. Alterations to the immune baseline of the pIgR KO mice may also be beneficial or detrimental during infection.…”

Differential Intestinal Mucosa Transcriptomic Biomarkers for Crohn’s Disease and Ulcerative Colitis

“…Studies conducted so far analyzing the expression levels of cytokines and transcription factors in mucosa revealed that CD has been associated with an impairment of Th1/Th17 response [ 8 ], whereas UC has been associated with a Th2/NKT cell response [ 9 ]. Other genes have been indicated as putative differential biomarkers, including α -defensin-5 [ 10 ], circadian genes [ 11 ], TNFAIP3, PIGR, TNF, and PIGR [ 12 ]. Other studies based on RNA-seq approaches revealed important transcriptomic differences between normal mucosa, noninflamed CD mucosa, and inflamed CD mucosa [ 13 ] as well as differences among colon biopsies from CD patients, UC patients, and non-IBD controls [ 4 ].…”

Identification and Validation of Potential Hub Genes Correlated With Ulcerative Colitis Through Integrated Bioinformatics Analysis

“…IL-8 is vital in the induction of colonic in ammation and has been implicated in the IBD disease activity [13]. The previous studies showed that in UC patients, CXCL8 was particularly upregulated in the in amed mucosa, relative to the non-in amed mucosa [14][15][16].The gene Deleted in Malignant Brain Tumors 1 (DMBT1), which is found in chromosome 10q25.3-q26.1, is regarded as a tumor suppressor because of its homologous deletions and downregulation in lung cancer, medulloblastoma, gastrointestinal cancers, and glioblastoma multiforme [17,18] The existing researches have con rmed the relationship between DMBT1 and UC. Treatment with IL-22 promoted DMBT1 expression by inducing the phosphorylation of STAT3 tyrosine, as well as activation of NF-κB, suggesting the IL-22/DMBT1 axis might play a vital function in UC pathophysiology [19].…”