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Calprotectin as an early biomarker of bacterial infections in critically ill patients: an exploratory cohort assessment
Section of Anaesthesia and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.ORCID iD: 0000-0002-6097-6318
Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden..
Section of Anaesthesia and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden..
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2017 (English)In: Criminology & Public Policy, ISSN 1441-2772, E-ISSN 1941-1006, Vol. 19, no 3, p. 205-213Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Calprotectin is the most abundant protein in the cytosolic fraction of neutrophils, and neutrophil degranulation is a major response to bacterial infections.

OBJECTIVES: To assess the value of plasma calprotectin as an early marker of bacterial infections in critically ill patients and compare it with the corresponding values for procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC).

METHODS: We measured daily plasma calprotectin levels in 110 intensive care unit patients using a newly developed turbidimetric assay run on clinical chemistry analysers. The likelihood of infection was determined according to the International Sepsis Forum criteria.

RESULTS: Overall, 58 patients (52.7%) developed a suspected or confirmed bacterial infection. Plasma calprotectin predicted such infections within 24 hours with an area under the receiver operating characteristics curve (ROC area) of 0.78 (95% CI, 0.68-0.89). The ROC area for calprotectin was significantly greater than the corresponding ROC areas for WBC (P < 0.001) and PCT (P = 0.02) but only marginally better than the ROC area for CRP (0.71; 95% CI, 0.68-0.89).

CONCLUSION: Plasma calprotectin appears to be a useful early marker of bacterial infections in critically ill patients, with better predictive characteristics than WBC and PCT.

Place, publisher, year, edition, pages
2017. Vol. 19, no 3, p. 205-213
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-329205ISI: 000408400800003PubMedID: 28866970OAI: oai:DiVA.org:uu-329205DiVA, id: diva2:1141241
Available from: 2017-09-14 Created: 2017-09-14 Last updated: 2018-10-15Bibliographically approved
In thesis
1. Avian antibodies applied in particle enhanced turbidimetric immunoassay: Developement of serum/plasma calprotectin immunoassay and its clinical performance as a marker for bacterial infections
Open this publication in new window or tab >>Avian antibodies applied in particle enhanced turbidimetric immunoassay: Developement of serum/plasma calprotectin immunoassay and its clinical performance as a marker for bacterial infections
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Calprotectin is a cytosolic protein in the granulocytes, consisting of S100A8 and S100A9. On the site of inflammation, the neutrophils release the cytosol as an inflammatory response. The circulating calprotectin concentration increases and can therefore be used as marker for neutrophil activation and inflammation.

To raise specific antibodies, it is crucial to immunize with pure calprotectin antigen. We purified calprotectin from human granulocytes by ion-exchange chromatography, dialysed it towards saline and concentrated it to required levels, suited for immunisation of the hens. The purified antigen solutions were assigned concentration values by the Biuret method and the purity was checked by SDS PAGE and size exclusion chromatography. The yield was approximately 2 mg purified antigens per unit of 450 ml blood.

A prototype calprotectin particle enhanced turbidimetric immunoassay was developed from the purified antigen and the affinity purified antibodies. The antigen was spiked into PBS to prepare calibrators and controls. The antibodies were coated to latex particles to prepare immunoparticles. The performance of the immunoassay was technically tested on a clinical chemistry analyser. LoQ, antigen excess, linearity, precision and calibration stability met the pre-set criteria.

In the production process of immunoparticles there are several factors affecting the performance of the assay. Investigating eight factors applying a Taguchi L12 screening, we experienced that conductivity and pH of conjugate buffer, coating grade and conductivity of dialysis buffer II affected the sensitivity and antigen excess the most.

The assay was used to measure clinical samples. Serum samples from elderly people aged 70+ were collected. Only patients with no infections were included to establish a reference interval for this patient group. The reference interval in serum was 0.3 mg/L to 2.5 mg/L for both genders. Furthermore, the plasma calprotectin immunoassay was tested clinically on critically ill patients to assess the ability of plasma calprotectin as an early marker for detection of bacterial infections. It showed promising results. Calprotectin was a better predictive marker for sepsis than procalcitonin and white blood cell count. Because some patients with an inflammation have low numbers of granulocytes, we examined the correlation between white blood cell count and the calprotectin levels in a group of patients with an inflammation. There was a weak correlation between the number of white blood cells and calprotectin concentration.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 54
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1507
Keywords
Sepsis, avian antibodies, calprotectin antigen, particle enhanced turbidimetric immunoassay.
National Category
Clinical Laboratory Medicine
Research subject
Clinical Chemistry
Identifiers
urn:nbn:se:uu:diva-363261 (URN)978-91-513-0480-9 (ISBN)
Public defence
2018-12-06, Robergssalen, ingång 40, Akademiska Sjukhuset,, Uppsala, 10:00 (Norwegian)
Opponent
Supervisors
Funder
The Research Council of Norway, 223022/O30
Available from: 2018-11-15 Created: 2018-10-15 Last updated: 2018-11-30

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