Mo1833 Clinical Characteristics of Crohn's Disease and Ulcerative Colitis Patients Who Switched From an anti-TNF-α Agent or Natalizumab to Vedolizumab or an Alternative anti-TNF-α

Saccharomyces boulardii ( Sb) is a probiotic yeast that has demonstrated efficacy in pilot studies in patients with inflammatory bowel disease (IBD). Microbial antigen handling by dendritic cells (DC) is believed to be of critical importance for immunity and tolerance in IBD. The aim was to characterize the effects of Sb on DC from IBD patients. Highly purified (>95%), lipopolysaccharide-stimulated CD1c+CD11c+CD123−myeloid DC (mDC) from patients with ulcerative colitis (UC; n = 36), Crohn's disease (CD; n = 26), or infectious controls (IC; n = 4) were cultured in the presence or absence of fungal supernatant from Sb ( SbS). Phenotype and cytokine production and/or secretion of IBD mDC were measured by flow cytometry and cytometric bead arrays, respectively. T cell phenotype and proliferation were assessed in a mixed lymphocyte reaction (MLR) with allogenic CD4+CD45RA+naïve T cells from healthy donors. Mucosal healing was investigated in epithelial wounding and migration assays with IEC-6 cells. SbS significantly decreased the frequency of CD40-, CD80-, and CD197 (CCR7; chemokine receptor-7)-expressing IBD mDC and reduced their secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6 while increasing IL-8. In the MLR, SbS significantly inhibited T cell proliferation induced by IBD mDC. Moreover, SbS inhibited TH1 (TNF-α and interferon-γ) polarization induced by UC mDC and promoted IL-8 and transforming growth factor-β-dependent mucosal healing. In summary, we provide novel evidence of synergistic mechanisms how Sb controls inflammation (inhibition of T cell costimulation and inflammation-associated migration and mobilization of DC) and promotes epithelial restitution relevant in IBD.

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The role of TNF-alpha gene (-238G/A and -308G/A) polymorphisms in the etiology and pathogenesis of inflammatory bowel diseases in various ethnic groups

Almanac of Clinical Medicine ◽

10.18786/2072-0505-2019-47-067 ◽

2019 ◽

Vol 47 (6) ◽

pp. 548-558

Author(s):

I. V. Zhilin ◽

E. Yu. Chashkova ◽

A. A. Zhilina ◽

B. S. Pushkarev ◽

N. S. Korotaeva

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Gene Polymorphism ◽

Ethnic Groups ◽

Small Sample ◽

Tnf Α ◽

Study Results ◽

Inflammatory Bowel

This literature review deals with specifics of the natural course of inflammatory bowel disease (IBD) in patients from various ethnic groups and -308G/A and -238G/A promoter polymorphisms in tumor necrosis factor-alpha (TNF-α) gene. The search in PubMed, Medline, Еlibrary.ru databases has led to identify in total 20 studies, including 2 meta-analyses, on the role of TNF-α-308G/A and -238G/A gene polymorphism in the etiology and pathophysiology of IBD. The TNF-α-308G/A polymorphism is associated with increased secretion of this proinflammatory cytokine, whereas the TNF-α-238G/A genotype is characterized by reduced TNF-α secretion. A number of studies have shown an association between TNF-α-308G/A gene polymorphism and severe course of IBD, requiring more active treatment of patients (cytostatics, corticosteroids, biological agents). Some investigators have found that the patients carriers of TNF-α-308G/A had a higher probability of surgical interventions. The association between TNF-α-308G/A and the phenotypic characteristics of IBD has been identified in studies performed in Europe, Asia, and Russia. The association of this polymorphism with the prevalence of ulcerative colitis has been proven in some studies, in particular, in the Asian population. Similar associations have been noted in few publications originating from Europe and North America, while some studies have found no links between TNF-α-308G/A, -238G/A, and the course of IBD. TNF-α-238G/A gene polymorphism has not shown any significance for the prevalence and course of ulcerative colitis and Crohn's disease. One can assume that the differences in the study results arising from one and the same geographical area are related to genetic heterogeneity of the study groups, phenotypic variances between the study subjects, as well as relatively small sample sizes. Currently, the search for genetic, biochemical and other prognostic criteria for IBD course is in progress. There are studies in progress to investigate the mechanisms of transformation of the genetic information into the particulars of ulcerative colitis and Crohn's disease manifestations, with consideration of ethnicity.

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Mo1835 Clinical Characteristics of Patients With Crohn's Disease or Ulcerative Colitis Treated With Vedolizumab - A Real-World Data Analysis

Gastroenterology ◽

10.1016/s0016-5085(16)32677-4 ◽

2016 ◽

Vol 150 (4) ◽

pp. S789

Author(s):

Huifang Liang ◽

Sudhakar Manne ◽

Jesse Shick ◽

Shawn Yu ◽

Gregory Fusco ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Data Analysis ◽

Crohn's Disease ◽

Real World ◽

Clinical Characteristics ◽

Real World Data ◽

World Data

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Probiotic Lactobacillus and Bifidobacterium Strains Counteract Adherent-Invasive Escherichia coli (AIEC) Virulence and Hamper IL-23/Th17 Axis in Ulcerative Colitis, but Not in Crohn’s Disease

Cells ◽

10.3390/cells9081824 ◽

2020 ◽

Vol 9 (8) ◽

pp. 1824

Author(s):

Gabriella Leccese ◽

Alessia Bibi ◽

Stefano Mazza ◽

Federica Facciotti ◽

Flavio Caprioli ◽

...

Keyword(s):

Ulcerative Colitis ◽

Dendritic Cells ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Immune Cells ◽

Intestinal Epithelial ◽

Healthy Donors ◽

Tnf Α ◽

Bowel Diseases ◽

Probiotic Strains

Hypersecretion of proinflammatory cytokines and dysregulated activation of the IL-23/Th17 axis in response to intestinal microbiota dysbiosis are key factors in the pathogenesis of inflammatory bowel diseases (IBD). In this work, we studied how Lactobacillus and Bifidobacterium strains affect AIEC-LF82 virulence mechanisms and the consequent inflammatory response linked to the CCR6–CCL20 and IL-23/Th17 axes in Crohn’s disease (CD) and ulcerative colitis (UC) patients. All Lactobacillus and Bifidobacterium strains significantly reduced the LF82 adhesion and persistence within HT29 intestinal epithelial cells, inhibiting IL-8 secretion while not affecting the CCR6–CCL20 axis. Moreover, they significantly reduced LF82 survival within macrophages and dendritic cells, reducing the secretion of polarizing cytokines related to the IL-23/Th17 axis, both in healthy donors (HD) and UC patients. In CD patients, however, only B. breve Bbr8 strain was able to slightly reduce the LF82 persistence within dendritic cells, thus hampering the IL-23/Th17 axis. In addition, probiotic strains were able to modulate the AIEC-induced inflammation in HD, reducing TNF-α and increasing IL-10 secretion by macrophages, but failed to do so in IBD patients. Interestingly, the probiotic strains studied in this work were all able to interfere with the IL-23/Th17 axis in UC patients, but not in CD patients. The different interaction mechanisms of probiotic strains with innate immune cells from UC and CD patients compared to HD suggest that testing on CD-derived immune cells may be pivotal for the identification of novel probiotic strains that could be effective also for CD patients.

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P711. Clinical characteristics of patients with Crohn’s disease or ulcerative colitis treated with vedolizumab: a real-world data analysis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjw019.830 ◽

2016 ◽

Vol 10 (suppl 1) ◽

pp. S466-S467

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Data Analysis ◽

Crohn's Disease ◽

Real World ◽

Clinical Characteristics ◽

Real World Data ◽

World Data

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Prevalent hypovitaminosis D in Crohn´s disease correlates highly with mediators of osteoimmunology

Clinical & Investigative Medicine ◽

10.25011/cim.v37i3.21382 ◽

2014 ◽

Vol 37 (3) ◽

Cited By ~ 5

Author(s):

Nikša Turk ◽

Zdenka Turk

Keyword(s):

Bone Mineral Density ◽

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bone Mineral ◽

Bone Disease ◽

Odds Ratio ◽

Mineral Density ◽

Tnf Α ◽

Significant Difference

Purpose: In the context of osteoimmunology in Crohn's disease, an association was hypothesized among vitamin D and members of the TNF-α family, known as the RANK (receptor-activator of nuclear factor- κB)-RANK ligand-osteoprotegerin pathway. Methods:This was a cross-sectional study of 95 patients with Crohn’s disease (80 with long-standing disease and 15 newly diagnosed, never treated) and two control groups (healthy volunteers, n=30; and ulcerative colitis patients, n=30). Spine and hip bone mineral density was measured by dual-energy x-ray absorptiometry. Serum 25-hydroxyvitamin-D3, TNF-α, IL-6, sRANKL, osteoprotegerin levels and biochemical markers of bone turnover were analyzed. Results: The precursor metabolite, 25(OH)D3, was measured in 95 young adult CD patients (47 men, 48 women; median age 30 years). A suboptimal 25(OH)D3 level was observed in 90% of CD patients, of whom 40% had a serious deficiency. There was no significant difference in 25(OH)D3 levels between CD patients and those with ulcerative colitis. Analysis revealed an association between 25(OH)D3 deficiency and the increased biogenesis of osteoclastically-active sRANKL (p=0.014) and the proinflammatory cytokines TNF-α (p=0.015) and IL-6 (p=0.029) . CD patients with low bone mineral density had a mean 25(OH)D3 (35±18 nmol/l) in the range of serious deficiency to insufficiency, whereas mean 25(OH)D3 was higher (49±28 nmol/l) in patients with healthy bone status, although levels were still inadequate (p=0.004). The logistic model reported low levels of 25(OH)D3 to be a significant predictor of bone disease [odds ratio=2.66(6.8), p < 0.009]. In the multivariable analysis, adjusted for several confounding factors, 25(OH)D3, sRANKL, IL-6 and TNF-α were independently associated with a likelihood of bone disease [odds ratio (range): 1.02(2.75); 1.09(3.71); 1.27(6.95) respectively, p=0.001]. Conclusion: The presented findings suggest that a 25(OH)D3 deficiency accompanying an inflammatory state in CD is a high risk condition for metabolic bone disease.

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New IBD Markers: Definition of Disease Heterogeneity

Canadian Journal of Gastroenterology ◽

10.1155/1995/940854 ◽

1995 ◽

Vol 9 (6) ◽

pp. 301-304

Author(s):

Stephan R Targan

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Serum Markers ◽

Treatment Modalities ◽

Mucosal Inflammation ◽

Disease Heterogeneity ◽

Clinical Phenotypes ◽

Tnf Α ◽

Different Types

There is emerging evidence that serum and mucosal markers differentiate Crohn's disease from ulcerative colitis; moreover, subgroups can be defined within each disease. Subgroups have been defined on the basis of genetic, serum and mucosal markers, and are associated with different clinical phenotypes. Antineutrophil cytoplasmic antibodies (ANCA) define subgroups of patients with both ulcerative colitis and Crohn's disease. A new serum marker, 20P-1, has been found in 60 to 70% of patients with Crohn's disease, 20% of ulcerative colitis patients and approximately 10% of the normal control population. The 20P-1 marker further stratifies the subgroups of patients defined by ANCA. In addition to serum markers, genes regulating production of the cytokine tumour necrosis factor (TNF)-α have been shown to be different across ulcerative colitis and Crohn's disease, and within the ulcerative colitis group. Serum markers may reflect differential mucosal inflammatory responses as is best shown by ANCA. B cell clones within the mucosa of 60 to 70% of patients with ulcerative colitis produce ANCA spontaneously. Studies currently underway demonstrate different TNF- α production within the mucosa of patients with Crohn's disease compared with ulcerative colitis patients. Correlation studies with TNF-α microsatellites (genes) are being performed. These markers are the focus of a trial using molecularly engineered products that are capable of inhibiting TNF-α to identify patients likely to respond to anti-TNF therapy. In this constantly evolving climate of understanding and treating inflammatory bowel disease, serum, mucosal and genetic markers as well as genetic associations are being formed to determine clinical phenotypes that may be differentially responsive to very selected treatment modalities. These advances highlight the likelihood that the various markers define different types of mucosal inflammation. The different types of mucosal inflammation will determine the response or resistance to certain types of therapeutic options.

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