Calprotectin as a biomarker for immune dysfunction and 28‑day mortality in sepsis

Circulating calprotectin: biomarker of immune dysfunction in sepsis - study results

Results from a post-hoc analysis of calprotectin in ImmunoSep randomised clinical trial has been presented at the International Symposium on Intensive Care and Emergency Medicine ISICEM in Brussels by investigators from the Hellenic Institute for the Study of Sepsis.¹

The study evaluates the potential role of circulating calprotectin (S100A8/A9) as a biomarker to improve immune dysfunction classification and identify septic patients who may benefit from precision immunotherapy. Calprotectin is a protein complex released predominantly by neutrophils and monocytes and is known to participate in both inflammatory activation and progression toward immune suppression in sepsis. 

Calprotectin analysis using the GCAL® assay

In a post‑hoc exploratory analysis, plasma calprotectin levels were measured in 559 of 672 screened patients using the GCAL^® Calprotectin, a particle‑enhanced turbidimetric immunoassay compatible with routine clinical chemistry analysers.

Immune phenotypes in Sepsis‑3

The ImmunoSep trial classified patients with Sepsis‑3 into immune dysfunction phenotypes using two established biomarkers: circulating ferritin and monocyte HLA-DR expression.

• Ferritin levels > 4,420 ng/mL → defined macrophage activation‑like syndrome (MALS)
• Ferritin ≤ 4,420 ng/mL + monocyte HLA‑DR < 5,000 → identified sepsis‑induced immunoparalysis (SII)

Patients who did not meet these criteria were categorised as having an unclassified immune state.

Key findings from the post-hoc exploratory analysis¹

• Patients with MALS or SII showed higher calprotectin levels
• ROC analysis identified 7.75 mg/L as a threshold that separated patients with immune dysfunction from those without a defined profile
  
  

Calprotectin and treatment response

Among patients randomised to treatment who had calprotectin levels of 7.75 mg/L or higher, precision immunotherapy - anakinra or recombinant interferon‑gamma, given alongside standard care - was associated with approximately 50% lower risk of 28‑day mortality compared with standard care plus placebo.

These results suggest that calprotectin may help identify septic patients who are more likely to benefit from targeted immunomodulatory therapy, and highlights the potential for translating these findings into routine clinical practice.¹

¹

Implications for precision medicine in sepsis

These findings indicate that calprotectin may add value as a rapid and accessible biomarker for:

• Identifying septic patients with immune dysregulation
• Supporting personalised treatment decisions
• Selecting patients who may benefit from precision immunotherapy

Combining immune phenotyping with routine laboratory biomarkers such as calprotectin represents a promising advance in the development of precision medicine approaches for sepsis care.¹

The results was presented as a poster at ISICEM 2026, Brussels, by investigators from the Hellenic Institute for the Study of Sepsis and collaborating institutions.

Advantages of GCAL® in routine clinical laboratories

Gentian GCAL^® Calprotectin Immunoassay provides several practical advantages that support clinical adoption:

• GCAL^®  is a turbidimetric assay that can be performed on standard clinical chemistry platforms
• Enabling integration into existing laboratory workflows.
• compatible with standard clinical chemistry analysers

Compared with more specialised biomarker assays, this approach offers several practical advantages, including: 

• Rapid turnaround time suitable for emergency and intensive care settings
• Cost‑effective implementation in existing workflows
• 24/7 availability as part of routine laboratory operations

This makes calprotectin testing feasible at scale in hospital laboratories, supporting timely decision‑making for critically ill patients.

 Let’s talk about GCAL® - Circulating calprotectin

Interested in implementing GCAL^® in your laboratory or clinical setting? Share your details and we will contact you to discuss next steps. You can also send an email to marketing@gentian.com. 

References:

1.  Alevizou A, Alevroudis I, Aidoni Z, Avgeri S, Giagtzoglou I, Agapitou T, et al. Evaluation of calprotectin as a proxy biomarker for sepsis immune dysfunction classification and 28-day mortality - P276. Presented at 45th International Symposium on Intensive Care and Emergency Medicine (ISICEM), Brussels, Belgium; 2026. 

* GCAL^® is CE-marked under the In Vitro Diagnostic Regulation (IVDR 2017/746, CE 0123). It is not cleared by the U.S. FDA and is not available for sale in the United States.

This website may contain information about products that are not registered for use in your country of residence and may not comply with applicable laws or regulations in that country. We do not take any responsibility for accessing such information in those circumstances.