In pursuit of novel biomarkers reflecting intestinal inflammation: temporal variability and phenotypic characterisation of serum calprotectin and lactoferrin

Liselot Koelman, Tilman Grune, Andreas F. H. Pfeiffer, Natalia N. Rudovich, Romina di Giuseppe, Krasimira Aleksandrova


Background: Calprotectin and lactoferrin are emerging biomarkers associated with intestinal inflammation. Yet, little is known about the temporal variability and phenotypic characteristics of their serum measurements in human cohorts.
Methods: We assessed the within-person variation of serum calprotectin and lactoferrin concentrations measured on two occasions over a 4-month period in 207 healthy participants. We used intraclass correlation coefficients (ICCs) as a measure of reliability. We furthermore explored cross-sectional associations of calprotectin and lactoferrin with measures of anthropometry and inflammatory biomarkers using Spearman correlations and multivariable-adjusted linear regression analyses.
Results: Median serum concentrations of first and second measurements of calprotectin were 1,494 ng/mL [interquartile range (IQR): 1,123–2,029)] and 1,648 ng/mL (IQR: 1,139–2,486), and of lactoferrin were 455.9 ng/mL (IQR: 304.8–620.4) and 517.6 ng/mL (IQR: 352.5–734.2), respectively. In reliability analysis we observed reasonable levels of reliability for lactoferrin and calprotectin (ICC: 0.62, 95% CI: 0.51, 0.71; 0.38, 95% CI: 0.26, 0.49, respectively). Calprotectin and lactoferrin were positively correlated with each other [Rho: 0.55 (95% CI: 0.43, 0.65)], and anthropometry measures [body mass index (BMI): calprotectin, 0.14 (0.00, 0.27); lactoferrin, 0.16 (0.00, 0.30); waist circumference (WC): calprotectin, 0.16 (0.02, 0.29); lactoferrin, 0.10 (−0.06, 0.25)] and biomarkers of inflammation [interleukin-6: calprotectin, 0.34 (0.21, 0.46); lactoferrin, 0.31 (0.16, 0.44); C-reactive protein: calprotectin, 0.41 (0.26, 0.53); lactoferrin, 0.21 (0.05, 0.36); lipocalin-2: calprotectin, 0.49 (0.38, 0.59); lactoferrin, 0.75 (0.67, 0.81)]. Lipocalin-2 explained largest variation in calprotectin (23.4%) and lactoferrin (54.6%).
Conclusions: These findings suggest serum calprotectin and lactoferrin as reliable biomarkers reflecting the activity and size of an inflammatory process in the gut.