A Pilot Study Evaluating Novel Urinary Biomarkers for Crohn’s Disease

Ho, Shaun S C; Wall, Catherine; Gearry, Richard; Keenan, Jacqueline I.

doi:10.1159/000510682

Cited by 6 publications

(15 citation statements)

References 37 publications

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“…Interestingly, circulating IL-8, a pro-inflammatory cytokine, was strongly influenced by ancestry (6% of children had Pakistani ancestry) in our cohorts (25% of variance explained). IL-8 was previously found to be influenced by genetic polymorphisms in an eastern Indian population, potentially driving individual variations in the host’s immune response, in particular to infectious diseases [ 64 ]. Intra-individual factors such as hours of fasting and having a cold gave the expected results: insulin appeared to be the only protein significatively influenced by the hours of fasting and CRP was associated with having a cold.…”

Section: Discussionmentioning

confidence: 99%

“…Variations in omics profiles due to factors such as BMI, age, physical activity, fasting time and sampling conditions need to be well characterized in order to interpret subtle changes related to environmental exposures such as air pollution or endocrine-disrupting chemicals, the ultimate goal of recent exposome initiatives [60]. Omics measurements in our study are of great clinical relevance as they provide the basis for the discovery of new biomarkers of multiple medical conditions such as cancer, heart disease, neurological disorders or inflammatory diseases [61][62][63][64]. Here, we provide insight into which omics features are stable within individuals and demonstrate sufficient interindividual variation in order to reduce chance findings when conducting epidemiological studies with follow-up for disease outcomes [16].…”

Section: Discussionmentioning

confidence: 99%

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Variability of multi-omics profiles in a population-based child cohort

Hernández-Ferrer

Bustamante

et al. 2021

BMC Med

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Background Multiple omics technologies are increasingly applied to detect early, subtle molecular responses to environmental stressors for future disease risk prevention. However, there is an urgent need for further evaluation of stability and variability of omics profiles in healthy individuals, especially during childhood. Methods We aimed to estimate intra-, inter-individual and cohort variability of multi-omics profiles (blood DNA methylation, gene expression, miRNA, proteins and serum and urine metabolites) measured 6 months apart in 156 healthy children from five European countries. We further performed a multi-omics network analysis to establish clusters of co-varying omics features and assessed the contribution of key variables (including biological traits and sample collection parameters) to omics variability. Results All omics displayed a large range of intra- and inter-individual variability depending on each omics feature, although all presented a highest median intra-individual variability. DNA methylation was the most stable profile (median 37.6% inter-individual variability) while gene expression was the least stable (6.6%). Among the least stable features, we identified 1% cross-omics co-variation between CpGs and metabolites (e.g. glucose and CpGs related to obesity and type 2 diabetes). Explanatory variables, including age and body mass index (BMI), explained up to 9% of serum metabolite variability. Conclusions Methylation and targeted serum metabolomics are the most reliable omics to implement in single time-point measurements in large cross-sectional studies. In the case of metabolomics, sample collection and individual traits (e.g. BMI) are important parameters to control for improved comparability, at the study design or analysis stage. This study will be valuable for the design and interpretation of epidemiological studies that aim to link omics signatures to disease, environmental exposures, or both.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Variability of multi-omics profiles in a population-based child cohort

Hernández-Ferrer

Bustamante

et al. 2021

BMC Med

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“…A basal level of urinary I-FABP represents the physiological turnover rate of the epithelium, whilst its increment may indicate enterocytes cell damage. In sepsis and IBD, the increased urinary concentration of I-FABP has been confirmed as a reliable biomarker and predictor of disease reactivation, worse prognosis and clinical complications (Ho et al, 2020). Therefore, our study assessed the levels of I-FABP in hospitalised patients with SARS-CoV-2 infection and investigated its role as a predictor of disease severity and poor prognosis.…”

Section: Short Communicationmentioning

confidence: 98%

Clinical investigation of intestinal fatty acid-binding protein (I-FABP) as a biomarker of SARS-CoV-2 infection

Saia

Giusti

Luis-Silva

et al. 2021

International Journal of Infectious Diseases

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Objectives SARS-CoV-2 exhibits tropism for the gastrointestinal tract, however lesions in enterocytes and their correlation with disease severity and patient prognosis are still unknown. Methods SARS-CoV-2 patients were enrolled in five medical centres in the São Paulo State, Brazil. Clinical characteristics and laboratory findings of patients were recorded. At admission, 7 th and 14 th day of hospitalisation, plasma and urine samples were collected. The levels of cytokines (IFN-γ, IL-6 and TNF-α) and the biomarker intestinal fatty acid-binding protein (I-FABP) were measured. Results COVID-19 patients displayed ≈48-, 74- and 125-fold increased urinary I-FABP levels at admission ( n= 283; p <0.001), 7 th ( n =142; p <0.01) and 14 th day ( n =75; p <0.01) of hospitalisation, respectively. Critically ill patients and nonsurvivors showed higher I-FABP concentrations compared to those in the infirmary and survivors, respectively, within the same hospital stay periods. At admission, infected patients demonstrated enhanced production of plasma IFN-γ and IL-6. The ROC curve suggested I-FABP as a biomarker for disease severity of COVID-19 at admission ( p <0.0001; Youden index=6.89; AUC=0.699). Patients with I-FABP≥6.89 showed higher IL-6 and C-reactive protein levels ( p <0.001) at admission, as well as prolonged length of hospital stay. Conclusions Our findings revealed damage to enterocytes in SARS-CoV-2 infection, which is associated to illness severity, poor prognosis and exacerbated inflammatory response.

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“…Previous reports have shown that patients with IBD and coeliac disease have significantly higher concentration of circulating iFABP compared with healthy controls (Controls) but evidence has not always been consistent (Additional file 1 : Table 1 ) [ 15 – 27 ]. The concentration of iFABP in patients with Crohn’s disease has also been shown to correlate with the pro-inflammatory cytokine tumour necrosis factor (TNF)-α and significantly decrease during treatment with anti-TNF-α therapy [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…There is currently limited literature which has explored responses of iFABP to therapy in patients with Crohn’s disease and coeliac disease and whether these biomarkers might be useful for monitoring changes in small bowel disease activity, and as biomarkers of GFD compliance in the latter group. Furthermore, the value of urinary compared to blood measurements of iFABP, with the former matrix potentially allowing non-invasive and remote monitoring of disease activity, has only been explored in a recent pilot study in adult patients with Crohn’s disease [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn’s disease

et al. 2022

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Background There is a clinical need to develop biomarkers of small bowel damage in coeliac disease and Crohn’s disease. This study evaluated intestinal fatty acid binding protein (iFABP), a potential biomarker of small bowel damage, in children with coeliac disease and Crohn’s disease. Methods The concentration iFABP was measured in plasma and urine of children with ulcerative colitis, coeliac disease, and Crohn’s disease at diagnosis and from the latter two groups after treatment with gluten free diet (GFD) or exclusive enteral nutrition (EEN), respectively. Healthy children (Controls) were also recruited. Results 138 children were recruited. Plasma but not urinary iFABP was higher in patients with newly diagnosed coeliac disease than Controls (median [Q1, Q3] coeliac disease: 2104 pg/mL 1493, 2457] vs Controls: 938 pg/mL [616, 1140], p = 0.001). Plasma or urinary iFABP did not differ between patients with coeliac on GFD and Controls. Baseline iFABP in plasma decreased by 6 months on GFD (6mo GFD: 1238 pg/mL [952, 1618], p = 0.045). By 12 months this effect was lost, at which point 25% of patients with coeliac disease had detectable gluten in faeces, whilst tissue transglutaminase IgA antibodies (TGA) continued to decrease. At diagnosis, patients with Crohn’s disease had higher plasma iFABP levels than Controls (EEN Start: 1339 pg/mL [895, 1969] vs Controls: 938 pg/mL [616, 1140], p = 0.008). iFABP did not differ according to Crohn’s disease phenotype. Induction treatment with EEN tended to decrease (p = 0.072) iFABP in plasma which was no longer different to Controls (EEN End: 1114 pg/mL [689, 1400] vs Controls: 938 pg/mL [616, 1140], p = 0.164). Plasma or urinary iFABP did not differ in patients with ulcerative colitis from Controls (plasma iFABP, ulcerative colitis: 1309 pg/mL [1005, 1458] vs Controls: 938 pg/mL [616, 1140], p = 0.301; urinary iFABP ulcerative colitis: 38 pg/mg [29, 81] vs Controls: 53 pg/mg [27, 109], p = 0.605). Conclusions Plasma, but not urinary iFABP is a candidate biomarker with better fidelity in monitoring compliance during GFD than TGA. The role of plasma iFABP in Crohn’s disease is promising but warrants further investigation. Trial registration: Clinical Trials.gov, NCT02341248. Registered on 19/01/2015.

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A Pilot Study Evaluating Novel Urinary Biomarkers for Crohn’s Disease

Cited by 6 publications

References 37 publications

Variability of multi-omics profiles in a population-based child cohort

Variability of multi-omics profiles in a population-based child cohort

Clinical investigation of intestinal fatty acid-binding protein (I-FABP) as a biomarker of SARS-CoV-2 infection

Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn’s disease

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