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

AbstractIn the search for improved stool biomarkers for inflammatory bowel disease (IBD), an aptamer-based screen of 1129 stool proteins was conducted using stool samples from an IBD cohort. Here we report that of the 20 proteins subsequently validated by ELISA, stool Ferritin, Fibrinogen, Haptoglobin, Hemoglobin, Lipocalin-2, MMP-12, MMP-9, Myeloperoxidase, PGRP-S, Properdin, Resistin, Serpin A4, and TIMP-1 are significantly elevated in both ulcerative colitis (UC) and Crohn’s disease (CD) compared to controls. When tested in a longitudinal cohort of 50 UC patients at 4 time-points, fecal Fibrinogen, MMP-8, PGRP-S, and TIMP-2 show the strongest positive correlation with concurrent PUCAI and PGA scores and are superior to fecal calprotectin. Unlike fecal calprotectin, baseline stool Fibrinogen, MMP-12, PGRP-S, TIMP-1, and TIMP-2 can predict clinical remission at Week-4. Here we show that stool proteins identified using the comprehensive aptamer-based screen are superior to fecal calprotectin alone in disease monitoring and prediction in IBD.

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AB0702 THE FREQUENCY OF INFLAMMATORY BOWEL DISEASES IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3798 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1647.2-1647

Author(s):

G. Lukina ◽

P. Kulakova ◽

N. Savenkova ◽

E. Volnukhin ◽

A. Kovshik ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Longitudinal Study ◽

Ankylosing Spondylitis ◽

Disease Activity ◽

Bowel Disease ◽

Rapid Test ◽

Neutrophil Infiltration ◽

Fecal Calprotectin ◽

High Disease Activity ◽

Inflammatory Bowel

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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Fecal Lipocalin-2 as a Sensitive and Noninvasive Biomarker in the TNBS Crohn’s Inflammatory Bowel Disease Model

Toxicologic Pathology ◽

10.1177/0192623316665927 ◽

2016 ◽

Vol 44 (8) ◽

pp. 1084-1094 ◽

Cited By ~ 4

Author(s):

Heidi Hsieh ◽

Jeffrey Morin ◽

Cyndi Filliettaz ◽

Rao Varada ◽

Shelby LaBarre ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Body Weight ◽

Bowel Disease ◽

Saline Water ◽

Disease Model ◽

Recovery Phase ◽

Lipocalin 2 ◽

Trinitrobenzenesulfonic Acid ◽

Noninvasive Biomarker ◽

Inflammatory Bowel

Colitis induced by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) has been used as a model for Crohn’s disease (CD) of inflammatory bowel disease (IBD). Lipocalin-2 (Lcn-2) is an emerging and clinically relevant biomarker of IBD. We investigated the performance of serum and fecal Lcn-2 in the TNBS model of colitis. Female, 7-week-old, BALB/c mice were administered intrarectally phosphate-buffered saline/water or 30% ethanol (vehicle control groups) for 5 days or TNBS for 5 days followed by a 28-day recovery phase. Serum and fecal levels of Lcn-2 were quantified, and effects on body weight, clinical scores, colon weight and length, gross pathology, and histopathology were investigated. Increased serum Lcn-2 levels correlated only with marked to severe inflammation. A clear differentiation in Lcn-2 fecal levels between TNBS-treated and vehicle-treated control mice was most noticeable on days 2 and 3. There was a strong correlation between body weight change, histopathologic scores of inflammation, and/or fecal Lcn-2 levels on days 2 and 5. Both serum and fecal Lcn-2 levels declined over time as the colonic mucosa recovered. Fecal Lcn-2 was found to be a more sensitive biomarker (vs. serum Lcn-2) and was able to discriminate mild, moderate, and severe colonic inflammation.

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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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