Fecal Lactoferrin Is a Sensitive and Specific Marker of Disease Activity in Children and Young Adults With Inflammatory Bowel Disease

Harvard University, Cambridge, Massachusetts, United States
Journal of pediatric gastroenterology and nutrition (Impact Factor: 2.63). 05/2007; 44(4):414-22. DOI: 10.1097/MPG.0b013e3180308d8e
Source: PubMed


Fecal lactoferrin (FLA) is a neutrophil-derived surrogate marker of intestinal inflammation that is elevated in patients with inflammatory bowel disease. However, the correlation between FLA levels and serological markers of disease activity has not been previously reported, to our knowledge. In the present study we evaluated the ability of FLA levels to reflect disease activity in pediatric patients with inflammatory bowel disease. We further assessed the relationship between FLA levels and customary laboratory and clinical measures of inflammation.
Fecal specimens were collected from 148 consecutive pediatric patients (79 with Crohn disease, 62 with ulcerative colitis, and 7 with irritable bowel syndrome) and 22 healthy control individuals. Lactoferrin was measured by enzyme-linked immunosorbent assay (IBD-SCAN, TECHLAB, Inc). Disease activity was assessed at the time of sample provision by laboratory measures (including erythrocyte sedimentation rate [ESR] and albumin) and previously validated disease activity indices (Pediatric Crohn Disease Activity Index, Kozarek, Harvey Bradshaw Activity Index).
Lactoferrin levels were significantly higher in patients with ulcerative colitis (1880 +/- 565 microg/mL) (mean +/- SE) or Crohn disease (1701 +/- 382 microg/mL) than in healthy control individuals under 21 years of age (1.17 +/- 0.47 microg/mL, P < 0.001). Lactoferrin levels correlated significantly with ESR, hematocrit, albumin, and platelet count (P < 0.001). Receiver operating characteristic curve analysis revealed that FLA levels were comparable to ESR in detecting patients with clinically active disease (P < 0.001). Patients who experienced a clinical flare within 2 months of specimen collection displayed higher lactoferrin levels (845 +/- 452 microg/mL) than did those who remained in clinical remission (190 +/- 90 microg/mL, P = 0.003).
Data presented here demonstrate that FLA is a sensitive and specific biochemical marker of inflammation for use in the diagnosis and interval assessment of pediatric patients with IBD, and its level correlates well with both clinical disease activity indices and ESR. Elevated levels of FLA may also identify patients at greater risk for the development of subsequent clinical flares.

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Available from: Paul A Rufo, Feb 10, 2015
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    • "As our aim was to observe the diagnostic performance of FL in differentiating IBD from IBS, our meta-analysis included 1012 patients, 609 with IBD, 381 with IBS and 22 healthy volunteers. Of the seven included studies, one measured FL solely in children and young adults [10], three measured FL in both children and adults [12-14], and the other three measured FL in adults only [3,11,15]. All seven studies used a commercially available enzyme-linked immunosorbent assay (IBD-SCAN®, Techlab, Blacksburg, VA, USA) to measure FL. "
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    ABSTRACT: Background To perform a meta-analysis evaluating the diagnostic ability of fecal lactoferrin (FL) to distinguish inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). Methods The Medline, EMBASE, Web of Science, Cochrane library and CNKI databases were systematically searched for studies that used FL concentrations to distinguish between IBD and IBS. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model. Results Seven studies, involving 1012 patients, were eligible for inclusion. In distinguishing IBD from IBS, FL had a pooled sensitivity of 0.78 (95% confidence interval [CI]: 0.75, 0.82), a specificity of 0.94 (95% CI: 0.91, 0.96), a positive likelihood ratio of 12.31 (95% CI: 5.93, 29.15), and a negative likelihood ratio of 0.23 (95% CI: 0.18, 0.29). The area under the summary receiver-operating characteristic curve was 0.94 (95% CI: 0.90, 0.98) and the diagnostic odds ratio was 52.65 (95% CI: 25.69, 107.91). Conclusions FL, as a noninvasive and simple marker, is useful in differentiating between IBD and IBS.
    Full-text · Article · Jul 2014 · BMC Gastroenterology
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    • "In addition, fecal lactoferrin showed good correlation to disease activity (endoscopic and histopathologic) and was 100% specific in ruling out IBS (46). Using an established cutoff point of 7.25 μg/mL for patients with IBD (48), similar findings of elevated fecal lactoferrin in pediatric patients with UC (1880 ± 565 μg/mL) and CD (1701 ± 382 μg/mL) compared to healthy controls (1.17 ± 0.47 μg/mL; P < 0.001) were observed (49). Fecal lactoferrin also correlated well with clinical activity indices and erythrocyte sedimentation rate (ESR) (49). "
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    ABSTRACT: The identification of various fecal biomarkers has provided insight into the intestinal milieu. Most of these markers are associated with the innate immune system of the gut, apart from the more novel M2-pyruvate kinase. The innate immunity of the gut plays a role in maintaining a fine balance between tolerance to commensal bacteria and immune response to potential pathogens. It is a complex system, which comprises of multiple elements, including antimicrobial peptides (e.g., defensins, cathelicidins, lactoferrin, and osteoprotegerin), inflammatory proteins (e.g., calprotectin and S100A12), and microbial products (e.g., short-chain fatty acids). Dysfunction of any component can lead to the development of intestinal disease, and different diseases have been associated with different fecal levels of these biomarkers. Each fecal biomarker provides information on specific biological and disease processes. Therefore, stool quantification of these biomarkers provides a non-invasive method to define potential pathways behind the pathogenesis of diseases and can assist in the assessment and diagnosis of various gastrointestinal conditions. The abovementioned fecal biomarkers and their role in intestinal health and disease will be reviewed in this paper with a pediatric focus.
    Full-text · Article · Jan 2014 · Frontiers in Pediatrics
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    • "Biomarkers that help determine the “inflammatory status” in the intestine of a CDI patient potentially help predict the severity of CDI and possibly help direct the choice of antibiotic therapy [16]. Fecal lactoferrin is a biomarker for intestinal inflammation and has been evaluated in both infectious diarrhea and inflammatory bowel disease [9, 11, 16, 30–32, 34, 38]. Previous studies have demonstrated that elevated lactoferrin occurs in patients with C. difficile disease [1, 17, 25, 39]. "
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    ABSTRACT: We evaluated blood and fecal biomarkers as indicators of severity in symptomatic patients with confirmed Clostridium difficile infection (CDI). Recruitment included patients with CDI based on clinical symptoms and supporting laboratory findings. Disease severity was defined by physician's assessment and blood and fecal biomarkers were measured. Toxigenic culture done using spore enrichment and toxin B detected by tissue culture were done as confirmatory tests. Polymerase chain reaction (PCR) ribotyping was performed on each isolate. There were 98 patients recruited, with 85 (87 %) confirmed cases of toxigenic CDI (21 severe, 57 moderate, and seven mild), of which 68 (80 %) were also stool toxin-positive. Elevated lactoferrin (p = 0.01), increased white blood cell (WBC) count (p = 0.08), and low serum albumin (p = 0.03) were all associated with the more severe cases of CDI. Ribotype 027 infection accounted for 71 % of severe cases (p < 0.01) and patients with stool toxin had significantly higher lactoferrin levels and WBC counts (p < 0.05). Our findings show that elevated fecal lactoferrin, along with increased WBC count and low serum albumin, were associated with more severe CDI. In addition, patients infected with ribotype 027 and those with stool toxin had significantly higher fecal lactoferrin and WBC counts.
    Full-text · Article · Jun 2013 · European Journal of Clinical Microbiology
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