Kristina Sejersen: Analysis of calprotectin as an early marker for bacterial infection and inflammation

Abstract

Calprotectin, a calcium-binding protein complex of S100A8 and S100A9, is abundant in neutrophils and released upon their activation. It has emerged as a potential biomarker for several inflammatory conditions, including respiratory infections, sepsis, and rheumatoid arthritis. With increasing concerns about antibiotic resistance, there is a need to accurately differentiate between bacterial and viral infections for better treatment decisions.

This thesis investigates the diagnostic performance of calprotectin in respiratory tract infections, its activation kinetics following inflammatory stimuli, its role as a biomarker in rheumatoid arthritis, and to compare total calprotectin levels with its subunits in intensive care unit (ICU) patients with sepsis. The studies included patients with respiratory infections, post-operative inflammation, rheumatoid arthritis, and sepsis, measuring calprotectin levels in serum, plasma, and synovial fluid.

Results showed significantly higher calprotectin levels in bacterial infections compared to viral infections and healthy controls. It outperformed procalcitonin (PCT) and Heparin-binding protein (HBP) in distinguishing bacterial from viral respiratory infections, including mycoplasma. Calprotectin levels increased rapidly (within 2 hours) following inflammation, earlier than CRP and IL-6. In rheumatoid arthritis, serum calprotectin correlated strongly with inflammatory markers, particularly in anti-citrullinated protein antibodies (ACPA)-positive patients. In ICU patients, total calprotectin performed better than its subunits (S100A8 and S100A9) in differentiating sepsis from non-sepsis cases.

Calprotectin shows promise as a biomarker for early detection of bacterial infections and inflammation. Its rapid rise and superior ability to differentiate bacterial and viral infections highlight its potential to improve the management of respiratory infections and guide antibiotic use. However, further research is needed to standardise assays and fully understand its specificity in various clinical contexts.