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Role of Calprotectin in Human Health and Disease
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Role of Calprotectin in Human Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 5952

Special Issue Editors

Dr. Mats B. Eriksson

E-Mail Website1 Website2
Guest Editor
Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, 751 85 Uppsala, Sweden
Interests: anesthesiology; biomarkers; calprotectin; coagulation; cytokines; endotoxin; critical care medicine; inflammation; intensive care; intraosseous; leptin; point-of-care; SAPS3; sepsis; shock
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Anders O. Larsson

E-Mail Website
Guest Editor
Department of Medical Sciences, Clinical Chemistry, Uppsala University, 751 85 Uppsala, Sweden
Interests: endotoxin; Intensive Care; acute kidney injury; glomerular filtration rate markers; kidney tubular damage markers; cardiovascular risk markers; neutrophil activation markers; calprotectin
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

You are invited to contribute research on calprotectin, a pleiotropic molecule released in both acute and chronic inflammation, is a heterodimer of two mammalian calcium-binding proteins and is released from the cytoplasm of neutrophil granulocytes upon their activation. Calprotectin (S100A9/S100A8) is a member of the S100 protein family. Calprotectin, as a proinflammatory factor of innate immunity, is related to the endogenous damage-associated molecular pattern (DAMP) molecule via Toll-like receptor 4 activation.

Determination of calprotectin is a valuable clinical biomarker of inflammation. In inflammatory gastro-intestinal diseases, colonoscopy and histopathologic evaluation of bowel biopsy specimens are usually regarded as the gold standards for diagnosis and management of such diseases. However, colonoscopy and colon biopsy are not only costly, but occasionally associated with complications. Since fecal calprotectin may serve as a potential surrogate marker for colonoscopy, several clinical studies have focused on this issue. Furthermore, calprotectin may serve as a biomarker of disease activity in rheumatoid arthritis. Plasma calprotectin seems to be a promising biomarker in respiratory infections, allowing more precise diagnosis and selective use of antibiotics compared to other biomarkers. In critically ill patients with bacterial infections, plasma calprotectin seems to be a useful biomarker. Based on these findings, a health economic analysis of the predictive use of plasma calprotectin indicates that this biomarker has cost-saving and life-saving impacts. Calprotectin may rapidly be analyzed turbidimetrically.

Dr. Mats B. Eriksson
Prof. Dr. Anders O. Larsson
Guest Editors

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Keywords

  • acute phase reactants
  • analysis
  • bacterial infection
  • biomarker
  • calprotectin
  • critical care
  • inflammation
  • turbidimetric

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Published Papers (4 papers)

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Research

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14 pages, 3939 KiB  
Article
Evaluation of a Classifier Based on Calprotectin Concentration and Advanced Glycation End-Product Receptor as a Potential Biomarker for Abdominal Aortic Aneurysm
by Willy Hauzer, Paula Hauzer, Tomasz Klimek, Jan Gnus, Wojciech Witkiewicz and Natalia Jędruchniewicz
Int. J. Mol. Sci. 2025, 26(16), 7752; https://doi.org/10.3390/ijms26167752 - 11 Aug 2025
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Abstract
Calprotectin is a calcium-binding protein involved in inflammatory processes. In the context of abdominal aortic aneurysm (AAA), elevated levels of calprotectin may indicate immune system activation and chronic inflammation, which are among the mechanisms contributing to the development and progression of AAA. The [...] Read more.
Calprotectin is a calcium-binding protein involved in inflammatory processes. In the context of abdominal aortic aneurysm (AAA), elevated levels of calprotectin may indicate immune system activation and chronic inflammation, which are among the mechanisms contributing to the development and progression of AAA. The receptor for advanced glycation end-products (RAGE) is a receptor that binds various ligands, including advanced glycation end-products formed during the glycation of proteins and lipids under oxidative stress conditions. Activation of RAGE is associated with inflammatory processes, oxidative stress, and tissue remodeling, which may contribute to the weakening of the aortic wall and aneurysm formation. The main objective of this study was to evaluate the effectiveness of both biomarkers in distinguishing patients with abdominal aortic aneurysm. A total of 27 patients with diagnosed AAA were included in the study. The control group consisted of 27 patients without AAA. Plasma levels of calprotectin and sRAGE were measured in both groups. Statistical analysis included the Shapiro–Wilk test, Mann–Whitney U test, and the Hosmer-Lemeshow (H-L) test. The likelihood of having AAA was found to be over one hundred times greater in individuals classified into the AAA group based on a decision tree model using calprotectin and sRAGE levels, compared to those classified into the no-AAA group. Calprotectin concentration was identified as a stronger predictor of AAA than sRAGE. The optimal cut-off value for plasma calprotectin was determined as ≥1136 ng/mL, yielding a sensitivity of 81.5% and a specificity of 100.0% for discriminating AAA patients from controls. It may be beneficial in future studies to explore non-invasive approaches, such as measuring calprotectin levels in stool and sRAGE in urine, as a potential screening method for AAA. Monitoring the concentrations of these biomarkers in bodily fluids, as a non-invasive method, could support screening efforts for AAA. Full article
(This article belongs to the Special Issue Role of Calprotectin in Human Health and Disease)
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Review

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19 pages, 1298 KiB  
Review
Non-Invasive vs. Invasive Markers in Ulcerative Colitis: A Systematic Review of Intestinal Ultrasound, Biopsy, and Faecal Calprotectin
by Viviana Parra-Izquierdo, Juliette De Avila, Oscar Gómez, Nelson Barrero, Miguel Duarte and Consuelo Romero-Sánchez
Int. J. Mol. Sci. 2025, 26(17), 8129; https://doi.org/10.3390/ijms26178129 - 22 Aug 2025
Abstract
Accurate assessment of histological remission is a critical goal in the management of ulcerative colitis (UC); however, routine evaluation is hindered by the invasiveness of endoscopy and biopsy. Non-invasive alternatives like intestinal ultrasound (IUS) and faecal calprotectin (FC) show promise for monitoring mucosal [...] Read more.
Accurate assessment of histological remission is a critical goal in the management of ulcerative colitis (UC); however, routine evaluation is hindered by the invasiveness of endoscopy and biopsy. Non-invasive alternatives like intestinal ultrasound (IUS) and faecal calprotectin (FC) show promise for monitoring mucosal inflammation, though their ability to predict histological healing remains underexplored. This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of IUS, FC, and their combined use for detecting histologic remission in patients with UC. A comprehensive literature search identified two eligible studies comprising 72 patients. Pooled estimates for IUS demonstrated high sensitivity (0.84, 95% CI: 0.35–0.98) but variable specificity (0.78, 95% CI: 0.08–0.99), while FC alone exhibited high sensitivity (0.85, 95% CI: 0.72–0.92) with moderate specificity (0.60, 95% CI: 0.38–0.79). Notably, only one study assessed the combined diagnostic approach, reporting superior performance with sensitivity and specificity of 0.88 and 0.80, respectively. The certainty of the evidence was rated as moderate. These exploratory findings suggest that a multimodal, non-invasive approach combining IUS and FC may improve diagnostic accuracy in detecting histological remission in UC, potentially reducing reliance on invasive procedures. However, given the limited number of studies included and the high degree of heterogeneity, these results should be interpreted with caution. Further large-scale, methodologically robust studies are needed to validate these preliminary findings and establish standardized diagnostic protocols. Full article
(This article belongs to the Special Issue Role of Calprotectin in Human Health and Disease)
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25 pages, 1050 KiB  
Review
Calprotectin as a Biomarker for Infectious Diseases: A Comparative Review with Conventional Inflammatory Markers
by Kristina Sejersen, Mats B. Eriksson and Anders O. Larsson
Int. J. Mol. Sci. 2025, 26(13), 6476; https://doi.org/10.3390/ijms26136476 - 4 Jul 2025
Viewed by 1182
Abstract
Calprotectin, the most abundant cytosolic protein in neutrophils, is a S100A8/S100A9 heterodimer released during immune activation. It inhibits bacterial growth by binding to essential metal ions and contributes to inflammation and leukocyte migration. This review highlights calprotectin’s potential as a diagnostic marker for [...] Read more.
Calprotectin, the most abundant cytosolic protein in neutrophils, is a S100A8/S100A9 heterodimer released during immune activation. It inhibits bacterial growth by binding to essential metal ions and contributes to inflammation and leukocyte migration. This review highlights calprotectin’s potential as a diagnostic marker for bacterial infections and inflammation. Clinical trials demonstrate that calprotectin is at least as effective as C-reactive protein, procalcitonin, and white blood cell counts in predicting bacterial infections. The rapid elevation of calprotectin levels in the early stages of sepsis, pneumonia, brain injury, and transplant complications underscores its diagnostic value. Predictive use of calprotectin may reduce ICU stays, mortality, and costs. However, challenges remain, including assay standardization and bacterial–viral differentiation. Advanced methods, such as the particle-enhanced turbidimetric immunoassay, enable faster and more reliable measurements. While calprotectin shows promise, further standardization and clinical validation are necessary to optimize its diagnostic utility. Full article
(This article belongs to the Special Issue Role of Calprotectin in Human Health and Disease)
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14 pages, 1032 KiB  
Review
The Role of Calprotectin in the Diagnosis and Treatment of Inflammatory Bowel Disease
by Wenqian Wang, Wenfu Cao, Shenyun Zhang, Dapeng Chen and Lihong Liu
Int. J. Mol. Sci. 2025, 26(5), 1996; https://doi.org/10.3390/ijms26051996 - 25 Feb 2025
Cited by 4 | Viewed by 3643
Abstract
The management of inflammatory bowel disease (IBD), which is characterized by immunodeficiency, has attracted increasing attention, highlighting the necessity for more precise and streamlined diagnostic approaches in clinics. Calprotectin, an immune cell-derived protein with inherent anti-inflammatory and antimicrobial properties, plays a pivotal role [...] Read more.
The management of inflammatory bowel disease (IBD), which is characterized by immunodeficiency, has attracted increasing attention, highlighting the necessity for more precise and streamlined diagnostic approaches in clinics. Calprotectin, an immune cell-derived protein with inherent anti-inflammatory and antimicrobial properties, plays a pivotal role in immune regulation and intestinal homeostasis. Its expression levels are intricately linked to IBD activity, enabling differentiation between inflammatory and non-inflammatory states while predicting recurrence risks. As a non-invasive biomarker, fecal calprotectin (FC) and serum calprotectin (SC) analysis offers high reproducibility and clinical utility, facilitating both IBD diagnosis and real-time disease monitoring. Beyond its diagnostic specificity in distinguishing IBD from other gastrointestinal disorders, calprotectin also emerges as a promising therapeutic target, due to its dual role in modulating inflammatory pathways and interacting with the gut microbiota. With collaborative advancements in standardized detection protocols and innovative research methodologies, it is anticipated that calprotectin-based strategies will be integrated into mainstream clinical practice for IBD. Full article
(This article belongs to the Special Issue Role of Calprotectin in Human Health and Disease)
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