Best practices in DNA methylation: lessons from inflammatory bowel disease, psoriasis and ankylosing spondylitis

Background:Аnkylosing Spondylitis (AS) is closely associated with inflammatory bowel disease (IBD). About 6-46% of patients with IBD have various lesions of the musculoskeletal system [1]. 5-10% of patients with spondylarthritis (SpA) eventually develop IBD, with Crohn’s disease (CD) being more common than Ulcerative colitis (UC) [2]. Determining the level of fecal calprotectin (FC) is a study that allows to diagnose IBD. The concentration of FC directly depends on the neutrophil infiltration of the intestinal mucosa and has a direct connection with the activity of the inflammatory process [3]. It is known that level of FC increases in 2/3 of patients with AS and is closely related to parameters reflecting higher disease activity [4].Objectives:The aim of this study was to evaluate the frequency of IBD in patients with AS using an assessment of FC level.Methods:In the analysis were included 40 patients with AS, fulfilling the modified New York criteria, among them man -26 (65%), woman -14 (35%), mean age of patients was 41.2 ±10.5, mean disease duration - 13±8.8 years. All patients were examined with ESR, CRP, esophagogastroduodenoscopy, colonoscopy and quantitative analysis of the fecal calprotectin levels using the method of lateral immunochromatography with the BUHLMANN Quantum Blue rapid test. Standart range: 100-1800 µg /g.Results:All patients had a high disease activity, mean BASDAI was 5.2 ± 1.7, mean ASDAS CRP 3.8 ± 1.1. 35 patients (87.5 %) had FC level more than 100 µg / g, the remaining 5 patients (12.5%) less than 100 µg /g. 12 patients (30 %) had FC level more than 1,800 µg / g, 23 (57.5 %) from 101 µg / g to 1800 µg / g. All patients with FC levels more than 100 µg / g showed an increase CRP (mean 28.4 mg / l) and ESR (mean 36.3 mm\h) levels. IBD were diagnosed in 9 cases (22.5%): 5 patients (12.5 %) with CD and 4 patients (10 %) - UC, in the remaining cases (77.5%) was no intestinal pathology.Conclusion:The results showed high frequency of IBD in patients with AS. Patients with high FC levels (more than 100 μg/g) had high disease activity (AS). In most cases, inflammatory bowel disease were diagnosed in patients with FC levels more than 100 µg/g.References:[1] Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001 Apr;96(4):1116-22.[2] Klingberg, E., Strid, H., Stahl, A.et al. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. Arthritis Res Ther 2017. 19(1):21[3] Cypers H, Varkas G, Beeckman S, et al. Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis. Annals of the Rheumatic Diseases. 2016. 75:1357-1362[4] Arzu Duran, Senol Kobak, Nazime Sen, et al. Fecal calprotectin is associated with disease activity in patients with ankylosing spondylitis. Bosnian Journal of Basic Medical Sciences. 2016. 16 (1):71-4Disclosure of Interests:Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Polina Kulakova: None declared, Nadezhda Savenkova: None declared, Evgeniy Volnukhin: None declared, Anton Kovshik: None declared, Elena Alexandrova: None declared, Alexandr Novikov: None declared

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Assessing DNA methylation in the developing human intestinal epithelium: potential link to inflammatory bowel disease

Mucosal Immunology ◽

10.1038/mi.2015.88 ◽

2015 ◽

Vol 9 (3) ◽

pp. 647-658 ◽

Cited By ~ 26

Author(s):

J Kraiczy ◽

K Nayak ◽

A Ross ◽

T Raine ◽

T N Mak ◽

...

Keyword(s):

Dna Methylation ◽

Inflammatory Bowel Disease ◽

Intestinal Epithelium ◽

Bowel Disease ◽

Potential Link ◽

Inflammatory Bowel ◽

Human Intestinal Epithelium

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Epigenetic Modifications of the Nuclear Factor Kappa B Signalling Pathway and its Impact on Inflammatory Bowel Disease

Current Pharmaceutical Design ◽

10.2174/1381612827666210218141847 ◽

2021 ◽

Vol 27 ◽

Author(s):

Stamatia Papoutsopoulou ◽

Barry J. Campbell

Keyword(s):

Dna Methylation ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Nuclear Factor Kappa B ◽

Intestinal Inflammation ◽

Alternative Pathway ◽

Current Evidence ◽

Nuclear Factor ◽

Nuclear Factor Kappa ◽

Inflammatory Bowel

Background: Inflammatory bowel disease (IBD) is a multifactorial condition influenced by the immune system, the intestinal microbiota, environmental factors, genetic and epigenetic factors. Genetic- and environment-induced dysregulation of the Nuclear Factor-kappa B (NF-κB) transcription factor pathway has been linked to IBD pathogenesis. Objective: To assess the current evidence in relation to the contribution of the classical and alternative NF-κB pathways in IBD and to discuss the epigenetic mechanisms that impact on NF-κB function. Methods: A Medline search for ‘NF-kappaB/NF-κB’, in combination with terms including ‘inflammatory bowel disease/IBD’, 'intestinal inflammation', ‘Crohn's disease’, ‘ulcerative colitis’, 'colitis'; ‘epigenetics’, ‘DNA methylation’, ‘histones’, ‘microRNAs/miRNAs’ and ‘short non-coding/long non-coding RNAs’ was performed. Results: Both NF-κB pathways contribute to the chronic inflammation underlying IBD by regulating the inflammatory immune responses and homeostasis of the intestinal epithelium (classical pathway) or regulating bowel inflammation and epithelial microfold (M) cell function (alternative pathway). DNA methylation is a common epigenetic modification in intestinal inflammation, including NFKB1 and RELA loci. Conversely, little is understood regarding epigenetic effects on genes encoding other NF-κB subunits, particularly those of the alternative pathway, and in the context of IBD. However, NF-κB interaction with chromatin modifiers is also seen to be an essential mechanism of regulation of downstream target genes relevant to NF-κB-mediated inflammatory responses. Conclusion: Further research is clearly warranted in this area, as understanding the cell-specific regulation of the NF-κB pathways will bring researchers into a position to achieve more efficient stratification of IBD patients, and more targeted and effective choice of treatment.

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Lipocalin 2 links inflammation and ankylosis in the clinical overlap of inflammatory bowel disease (IBD) and ankylosing spondylitis (AS)

Arthritis Research & Therapy ◽

10.1186/s13075-020-02149-4 ◽

2020 ◽

Vol 22 (1) ◽

Author(s):

Aifeng Lin ◽

Robert D. Inman ◽

Catherine J. Streutker ◽

Zhenbo Zhang ◽

Kenneth P. H. Pritzker ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Ankylosing Spondylitis ◽

Bowel Disease ◽

Lipocalin 2 ◽

Inflammatory Bowel

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Sulphasalazine-Induced Pseudomembranous Colitis

Canadian Journal of Gastroenterology ◽

10.1155/1991/420864 ◽

1991 ◽

Vol 5 (5) ◽

pp. 167-170 ◽

Cited By ~ 4

Author(s):

Hugh J Freeman ◽

Urs P Steinbrecher ◽

WC Peter Kwan ◽

Stephanie Ensworth

Keyword(s):

Inflammatory Bowel Disease ◽

Abdominal Pain ◽

Ankylosing Spondylitis ◽

Clostridium Difficile ◽

Bowel Disease ◽

Pseudomembranous Colitis ◽

Flexible Sigmoidoscopy ◽

Frequent Use ◽

Toxin Assay ◽

Inflammatory Bowel

An 18-year-old female with ankylosing spondylitis developed fever, abdominal pain and diarrhea on two occasions after starting sulphasalazine therapy. Flexible sigmoidoscopy revealed pseudomembranous colitis; fecal cultures were positive forClostridium difficile; andC difficiletoxin assay was positive. Despite the frequent use of sulphasalazine in the management of inflammatory bowel disease, this complication has been apparently rare. Clinicians should be wary of the onset of diarrhea in patients receiving sulphasalazine, whether for inflammatory bowel disease or other conditions.

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