Serum Calprotectin: A Novel Diagnostic and Prognostic Marker in Inflammatory Bowel Diseases

Kalla, Rahul; Kennedy, Nicholas A; Ventham, Nicholas T.; Boyapati, Ray; Adams, Alexander T.; Nimmo, Elaine R.; Visconti, M.; Drummond, Hazel E.; Ho, Gwo Tzer; Pattenden, Rebecca; Wilson, David C.; Satsangi, Jack

doi:10.1038/ajg.2016.342

Cited by 105 publications

(105 citation statements)

References 50 publications

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“…CALP is a potent activator of innate immunity mediated through Toll-like receptor 4 (9) and is primarily a product of neutrophils. Elevated serum CALP levels are associated with inflammatory diseases (10,11), while fecal CALP assays are widely used to differentiate inflammatory bowel disease from irritable bowel syndrome and ulcerative colitis (12). In the present study, we confirm that serum CALP levels are elevated in NHPs with respiratory infections caused by B. pseudomallei and examine the possibility of using CALP as a general biomarker for clinical responses during the acute and eradication phases of antibiotic treatment in human cases of melioidosis.…”

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confidence: 70%

Calprotectin as a Biomarker for Melioidosis Disease Progression and Management

et al. 2017

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Melioidosis is a neglected tropical disease that is caused by the bacterium Burkholderia pseudomallei and is underreported in many countries where the disease is endemic. A long and costly administration of antibiotics is needed to clear infections, and there is an unmet need for biomarkers to guide antibiotic treatment and increase the number of patients that complete therapy. We identified calprotectin as a lead biomarker of B. pseudomallei infections and examined correlations between this serum protein and the antibiotic treatment outcomes of patients with melioidosis. Serum levels of calprotectin and C-reactive protein were significantly higher in patients with melioidosis and nonmelioidosis sepsis than in healthy controls. Median calprotectin levels were higher in patients with melioidosis than in those with nonmelioidosis sepsis, whereas C-reactive protein levels were similar in both groups. Notably, intensive intravenous antibiotic treatment of patients with melioidosis resulted in lower levels of calprotectin and C-reactive protein (P Ͻ 0.0001), coinciding with recovery. The median percent reduction of calprotectin and C-reactive protein was 71% for both biomarkers after antibacterial therapy. In contrast, we found no significant differences in calreticulin levels between the two melioidosis treatment phases. Thus, reductions in serum calprotectin levels were linked to therapeutic responses to antibiotics. Our results suggest that calprotectin may be a sensitive indicator of melioidosis disease activity and illustrate the potential utility of this biomarker in guiding the duration of antibiotic therapy.

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confidence: 70%

Calprotectin as a Biomarker for Melioidosis Disease Progression and Management

et al. 2017

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“…Therapeutic escalation was defined as has been previously suggested (Kalla et al, 2016), and included the presence of at least one of the following events: starting a new immunomodulator or biological drug; switching immunomodulator; increasing biological dosage or shortening infusion interval; switching biological drug due to LOR; need to undergo bowel-related surgery.…”

Section: Methodsmentioning

confidence: 99%

Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation

et al. 2017

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Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62 μg/mL vs. 1.15 μg/mL, p = 0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3 μg/mL (HR = 0.119, p = 0.010), and increased for patients with fecal calprotectin (FC) level above 250 μg/g (HR = 9.309, p = 0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.

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“…We hypothesize that after airway triggering due to HA exposure, neutrophils are recruited to the airways and calprotectin is released from the activated neutrophils, resulting in leakage into the bloodstream. SC could be a sensitive marker of the degree of neutrophilic airway inflammation, although it may not be disease specific due to its presence and role in other neutrophilic inflammatory diseases . Therefore, SC might be useful in a set of markers to determine neutrophilic airway inflammation in asthmatics.…”

Section: Discussionmentioning

confidence: 99%

“…Serum biomarkers for neutrophilic inflammation have already been identified in other chronic inflammatory diseases. Serum calprotectin (SC) (S100A8/A9), highly present in the cytosol of neutrophils and released upon neutrophil activation, is elevated in serum of patients with inflammatory bowel disease (IBD), cystic fibrosis (CF) and rheumatoid arthritis (RA), which are also characterized by local neutrophilic inflammation . We hypothesized that asthmatic patients with neutrophilic airway inflammation may have increased SC levels due to leakage of calprotectin from the airways into the bloodstream.…”

Section: Introductionmentioning

confidence: 99%

Serum and sputum calprotectin, a reflection of neutrophilic airway inflammation in asthmatics after high‐altitude exposure

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et al. 2017

Clin Experimental Allergy

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Serum Calprotectin: A Novel Diagnostic and Prognostic Marker in Inflammatory Bowel Diseases

Abstract: A diagnostic and prognostic model that combines SC and other blood-based biomarkers accurately predicts the inflammatory burden in IBD and has the potential to predict disease and its outcomes. Our data warrant further detailed exploration and validation in large multicenter cohorts.

Cited by 105 publications

References 50 publications

Calprotectin as a Biomarker for Melioidosis Disease Progression and Management

Calprotectin as a Biomarker for Melioidosis Disease Progression and Management

Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic Escalation

Serum and sputum calprotectin, a reflection of neutrophilic airway inflammation in asthmatics after high‐altitude exposure

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