TNFSF13B, the gene that encodes the B-cell activating factor and B-lymphocyte stimulator (BAFF/BLyS), is expressed differently in the blood of Crohn's disease patients

2021 ◽  
Author(s):  
Kobi Decker ◽  
Bronte Morse

Crohn's disease and ulcerative colitis are examples of inflammatory bowel disorders (IBD) (1). We usedpublicly available microarray data to figure out how gene expression in the hematopoietic compartment ofCrohn's disease patients differs from healthy controls (2-4). We discovered that BAFF, also known as the Blymphocytestimulator (BLyS), encoded by the gene TNFSF13B (5), was differently expressed in the blood ofCrohn's Disease patients in two datasets (2, 3). BAFF was shown to be among the genes most differentlyexpressed in monocyte-derived macrophages from Crohn's Disease patients in a third dataset (4). Inindividuals with IBD, serum BAFF, fecal BAFF, and BAFF expression in the intestinal mucosa have all beenshown to be higher (6, 7). The expression of BAFF in the peripheral blood of Crohn's disease patients issimilarly enhanced, as seen below.

2020 ◽  
Author(s):  
Shahan Mamoor

Inflammatory bowel diseases (IBD) include Crohn’s Disease and Ulcerative Colitis (1). We mined published microarray data to understand how gene expression in the hematopoietic compartment of patients with Crohn’s Disease is most different from that of healthy controls (2-4). Across two datasets (2, 3), we found that BAFF, also known as the B-lymphocyte stimulator (BLyS), encoded by the gene TNFSF13B (5), was differentially expressed in the blood of patients with Crohn’s Disease . Analysis of a third dataset (4) revealed that BAFF was among the genes most differentially expressed in monocyte-derived macrophages from patients with Crohn’s Disease. Serum BAFF, fecal BAFF, and BAFF expression in the intestinal mucosa has been demonstrated to be increased in patients with IBD (6, 7). We show here that expression of BAFF in the peripheral blood of patients with Crohn’s Disease is also increased.


2011 ◽  
Vol 25 (5) ◽  
pp. 269-273 ◽  
Author(s):  
Charles N Bernstein ◽  
Hani El-Gabalawy ◽  
Michael Sargent ◽  
Carol J Landers ◽  
Patricia Rawsthorne ◽  
...  

BACKGROUND: First Nation populations in Canada have a very low incidence of inflammatory bowel disease (IBD). Based on typical infections in this population, it is plausible that the First Nations react differently to microbial antigens with a different antibody response pattern, which may shed some light as to why they experience a low rate of IBD.OBJECTIVE: To compare the positivity rates of antibodies known to be associated with IBD in Canadian First Nations compared with a Canadian Caucasian population.METHODS: Subjects with Crohn’s disease, ulcerative colitis (UC), rheumatoid arthritis (RA) (as an immune disease control) and healthy controls without a personal or family history of chronic immune diseases, were enrolled in a cohort study aimed to determine differences between First Nations and Caucasians with IBD or RA. Serum from a random sample of these subjects (n=50 for each of First Nations with RA, First Nations controls, Caucasians with RA, Caucasians with Crohn’s disease, Caucasians with UC and Caucasians controls, and as many First Nations with either Crohn’s disease or UC as could be enrolled) was analyzed in the laboratory for the following antibodies: perinuclear antineutrophil cytoplasmic antibody (pANCA), and four Crohn’s disease-associated antibodies including anti-Saccharomyces cerevisiae, the outer membrane porin C ofEscherichia coli, I2 – a fragment of bacterial DNA associated withPseudomonas fluorescens, and the bacterial flagellin CBir-1. The rates of positive antibody responses and mean titres among positive results were compared.RESULTS: For pANCA, First Nations had a positivity rate of 55% in those with UC, 32% in healthy controls and 48% in those with RA. The pANCA positivity rate was 32% among Caucasians with RA. The rates of the Crohn’s disease-associated antibodies for the First Nations and Caucasians were comparable. Among First Nations, up to one in four healthy controls were positive for any one of the Crohn’s disease-associated antibodies. First Nations had significantly higher pANCA titres in both the UC and RA groups than CaucasiansDISCUSSION: Although First Nation populations experience a low rate of IBD, they are relatively responsive to this particular antibody panel.CONCLUSIONS: The positivity rates of these antibodies in First Nations, despite the low incidence of IBD in this population, suggest that these antibodies are unlikely to be of pathogenetic significance.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1843 ◽  
Author(s):  
Kek Heng Chua ◽  
Jin Guan Ng ◽  
Ching Ching Ng ◽  
Ida Hilmi ◽  
Khean Lee Goh ◽  
...  

Crohn’s disease (CD) is a prominent type of inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal tract. CD is known to have higher prevalence in the Western countries, but the number of cases has been increasing in the past decades in Asia, including Malaysia. Therefore, there is a need to investigate the underlining causes of CD that may shed light on its prevention and treatment. In this study, genetic polymorphisms inNOD1(rs2075820),CXCL16(rs2277680),STAT6(rs324015) andTLR4(rs4986791) genes were examined in a total of 335 individuals (85 CD patients and 250 healthy controls) with PCR-RFLP approach. There was no significant association observed betweenNOD1rs2075820 andSTAT6rs324015 with the onset of CD in the studied cohort. However, the G allele ofCXCL16rs2277680 was found to have a weak association with CD patients (P= 0.0482;OR= 1.4310). TheTLR4rs4986791 was also significantly associated to CD. Both the homozygous C genotype (P= 0.0029;OR= 0.3611) and C allele (P= 0.0069;OR= 0.4369) were observed to confer protection against CD. On the other hand, the heterozygous C/T genotype was a risk genotype (P= 0.0015;OR= 3.1392). Further ethnic-stratified analysis showed that the significant associations inCXCL16rs2277680 andTLR4rs4986791 were accounted by the Malay cohort. In conclusion, the present study reported two CD-predisposing loci in the Malay CD patients. However, these loci were not associated to the onset of CD in Chinese and Indian patients.


2019 ◽  
Vol 14 (1) ◽  
pp. 118-129 ◽  
Author(s):  
Miranda G Kiernan ◽  
J Calvin Coffey ◽  
Shaheel M Sahebally ◽  
Paul Tibbitts ◽  
Emma M Lyons ◽  
...  

Abstract Background and Aims Faecal diversion is associated with improvements in Crohn’s disease but not ulcerative colitis, indicating that differing mechanisms mediate the diseases. This study aimed to investigate levels of systemic mediators of inflammation, including fibrocytes and cytokines, [1] in patients with Crohn’s disease and ulcerative colitis preoperatively compared with healthy controls and [2] in patients with Crohn’s disease and ulcerative colitis prior to and following faecal diversion. Methods Blood samples were obtained from healthy individuals and patients with Crohn’s disease or ulcerative colitis. Levels of circulating fibrocytes were quantified using flow cytometric analysis and their potential relationship to risk factors of inflammatory bowel disease were determined. Levels of circulating cytokines involved in inflammation and fibrocyte recruitment and differentiation were investigated. Results Circulating fibrocytes were elevated in Crohn’s disease and ulcerative colitis patients when compared with healthy controls. Smoking, or a history of smoking, was associated with increases in circulating fibrocytes in Crohn’s disease, but not ulcerative colitis. Cytokines involved in fibrocyte recruitment were increased in Crohn’s disease patients, whereas patients with ulcerative colitis displayed increased levels of pro-inflammatory cytokines. Faecal diversion in Crohn’s disease patients resulted in decreased circulating fibrocytes, pro-inflammatory cytokines, and TGF-β1, and increased IL-10, whereas the inverse was observed in ulcerative colitis patients. Conclusions The clinical effect of faecal diversion in Crohn’s disease and ulcerative colitis may be explained by differing circulating fibrocyte and cytokine responses. Such differences aid in understanding the disease mechanisms and suggest a new therapeutic strategy for inflammatory bowel disease.


2020 ◽  
Vol 21 (2) ◽  
pp. 676 ◽  
Author(s):  
Judith Abarca-Zabalía ◽  
Ma Isabel García ◽  
Alberto Lozano Ros ◽  
Ignacio Marín-Jiménez ◽  
Maria L. Martínez-Ginés ◽  
...  

The Th17 immune response plays a key role in autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). Expression of Th17-related genes in inflamed tissues has been reported in autoimmune diseases. However, values are frequently obtained using invasive methods. We aimed to identify biomarkers of MS in an accessible sample, such as blood, by quantifying the relative expression of 91 Th17-related genes in CD4+ T lymphocytes from patients with MS during a relapse or during a remitting phase. We also compared our findings with those of healthy controls. After confirmation in a validation cohort, expression of SMAD7 and S1PR1 mRNAs was decreased in remitting disease (–2.3-fold and –1.3-fold, respectively) and relapsing disease (–2.2-fold and –1.3-fold, respectively). No differential expression was observed for other SMAD7-related genes, namely, SMAD2, SMAD3, and SMAD4. Under-regulation of SMAD7 and S1PR1 was also observed in another autoimmune disease, Crohn’s disease (CD) (−4.6-fold, -1.6-fold, respectively), suggesting the presence of common markers for autoimmune diseases. In addition, expression of TNF, SMAD2, SMAD3, and SMAD4 were also decreased in CD (–2.2-fold, –1.4-fold, –1.6-fold, and –1.6-fold, respectively). Our study suggests that expression of SMAD7 and S1PR1 mRNA in blood samples are markers for MS and CD, and TNF, SMAD2, SMAD3, and SMAD4 for CD. These genes could prove useful as markers of autoimmune diseases, thus obviating the need for invasive methods.


2019 ◽  
Author(s):  
Shengbo Chen ◽  
Zhijun Li ◽  
Chen Li ◽  
Yi Liu ◽  
Fachao Zhi ◽  
...  

Abstract Background: Crohn’s disease (CD) is an inflammatory bowel (IBD) disease with variable and complex pathophysiology. The objective of the present study was to identify genome-wide gene expression profiles underlying the progression of CD. Methods: Surgery biopsies (n=48) were analyzed by Illumina cDNA-mediated annealing, selection, extension, and a ligation microarray process specifically designed for formalin-fixed, paraffin-embedded clinical samples. Tissue samples were collected from consecutive actively-involved and uninvolved sites from the same CD patient. The CD-involved and CD-uninvolved samples were compared with non-inflammatory bowel disease healthy controls. Results: CD patients’ uninvolved sites demonstrated an average gene expression between CD-involved patients and healthy controls suggesting the CD uninvolved site was unable to restore the full healthy control phenotype. In addition, peroxisome proliferator-activated receptors (PPAR) signaling-associated genes were involved in both CD involved and uninvolved sites, showing a stepwise decrease in the gene and protein expression of PPAR and downregulation of 3-hydroxy-3-methylglutaryl-CoA synthase 2, as confirmed by gene expression analysis and immunohistochemistry. Conclusions: The results of the present study provide evidence for clear differentiation of the two states, and in some cases repeated flares appeared chronically at the previous uninvolved locus.


1988 ◽  
Vol 27 (03) ◽  
pp. 83-86 ◽  
Author(s):  
B. Briele ◽  
F. Wolf ◽  
H. J. Biersack ◽  
F. F. Knapp ◽  
A. Hotze

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.


2020 ◽  
Vol 15 (3) ◽  
pp. 216-233 ◽  
Author(s):  
Maliha Naseer ◽  
Shiva Poola ◽  
Syed Ali ◽  
Sami Samiullah ◽  
Veysel Tahan

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.


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