Dataset Information

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

ABSTRACT:

Background

Little is known about the mechanisms underlying the clinical overlap between gut inflammation and joint ankylosis, as exemplified by the concurrence of inflammatory bowel diseases (IBD) and ankylosing spondylitis (AS). As dysbiosis may serve as a common contributor, the anti-microbial pleiotropic factor lipocalin 2 could be a potential mediator due to its roles in inflammation and bone homeostasis.

Methods

Baseline colonic pathology was conducted in the ank/ank mouse model. Serum lipocalin 2 was analyzed by ELISA, in ank/ank mutants versus C3FeB6-A/A^w-jwt/wt, in patients with concurrent AS-IBD, AS alone, IBD alone, or mechanical back pain, and in healthy controls. In the ank/ank mouse model, the expression of nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR?) was examined by real-time PCR. Intraperitoneal injection was done with the PPAR? agonist rosiglitazone or antagonist bisphenol A diglycidyl ether for four consecutive days. Serum levels of lipocalin 2 were examined on the sixth day.

Results

This study showed that the ank/ank mice with fully fused spines had concurrent colonic inflammation. By first using the ank/ank mouse model with progressive ankylosis and subclinical colonic inflammation, confirmed in patients with concurrent AS and IBD, elevated circulating lipocalin 2 levels were associated with the coexisting ankylosis and gut inflammation. The intracellular pathway of lipocalin 2 was further investigated with the ank/ank mouse model involving PPAR?. Colonic expression of PPAR? was negatively associated with the degree of gut inflammation. The PPAR? agonist rosiglitazone treatment significantly upregulated the serum levels of lipocalin 2, suggesting a potential regulatory role of PPAR? in the aberrant expression of lipocalin 2.

Conclusions

In summary, lipocalin 2 modulated by PPAR? could be a potential pathway involved in concurrent inflammation and ankylosis in AS and IBD.

SUBMITTER: Lin A

PROVIDER: S-EPMC7081573 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

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

Lin Aifeng A Inman Robert D RD Streutker Catherine J CJ Zhang Zhenbo Z Pritzker Kenneth P H KPH Tsui Hing Wo HW Tsui Florence W L FWL

Arthritis research & therapy 20200318 1

<h4>Background</h4>Little is known about the mechanisms underlying the clinical overlap between gut inflammation and joint ankylosis, as exemplified by the concurrence of inflammatory bowel diseases (IBD) and ankylosing spondylitis (AS). As dysbiosis may serve as a common contributor, the anti-microbial pleiotropic factor lipocalin 2 could be a potential mediator due to its roles in inflammation and bone homeostasis.<h4>Methods</h4>Baseline colonic pathology was conducted in the ank/ank mouse mo ...[more]

PMID: 32188494

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Project description:BackgroundPatients with ankylosing spondylitis (AS) are at increased risk of developing inflammatory bowel disease (IBD). We aimed to determine the variation in fecal calprotectin in AS over 5 years in relation to disease activity and medication and also to study the incidence of and predictors for development of IBD.MethodsFecal calprotectin was assessed at baseline (n = 204) and at 5-year follow-up (n = 164). The patients answered questionnaires and underwent clinical evaluations. At baseline and at 5-year follow-up, ileocolonoscopy was performed in patients with fecal calprotectin ≥500 mg/kg and ≥200 mg/kg, respectively. The medical records were checked for diagnoses of IBD during the follow-up period.ResultsFecal calprotectin >50 mg/kg was found in two-thirds of the patients at both study visits. In 80% of the patients, fecal calprotectin changed by <200 mg/kg between the two measuring points. Baseline fecal calprotectin was positively correlated with Ankylosing Spondylitis Disease Activity Score based on C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin at 5-year follow-up. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with higher fecal calprotectin, and 3-week cessation of NSAIDs resulted in a drop of a median 116 mg/kg in fecal calprotectin. The use of tumor necrosis factor (TNF) blockers was associated with lower fecal calprotectin at both visits, but the users of TNF receptor fusion proteins had significantly higher fecal calprotectin than users of anti-TNF antibodies at 5-year follow-up. The 5-year incidence of Crohn's disease (CD) was 1.5% and was predicted by high fecal calprotectin.ConclusionsFecal calprotectin was elevated in a majority of the patients and was associated with disease activity and medication at both visits. CD developed in 1.5% of the patients with AS, and a high fecal calprotectin was the main predictor thereof. The results support a link between inflammation in the gut and the musculoskeletal system in AS. We propose that fecal calprotectin may be a potential biomarker to identify patients with AS at risk of developing IBD.Trial registrationClinicalTrials.gov identifier: NCT00858819 . Registered 9 March 2009. Last updated 28 May 2015.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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