Circulating biomarkers of macrophage activation in different stages of chronic pancreatitis: A pilot study

Abstract Objectives Activation of type M2 macrophages has been implicated in the pathogenesis of chronic pancreatitis (CP). In a clinical pilot study, we investigated blood-based markers of macrophage activation at different stages of CP. Methods We performed a cross-sectional analysis of prospectively collected plasma samples from healthy controls and patients with suspected or definitive CP according to the M-ANNHEIM criteria. Plasma concentrations of soluble CD163 (sCD163), soluble CD206 (sCD206), and monocyte chemoattractant protein-1 (MCP-1) were analyzed using enzyme-linked immunosorbent assays. Group and pairwise comparisons of analytes were performed using regression models and area under the receiver operating curves (AUC-ROC). Results In total, 73 subjects with CP (28 suspected CP and 45 definitive CP) and 40 controls were included. Compared to controls, the median plasma concentrations of sCD163 (p = 0.019) and sCD206 (p = 0.033) were elevated in patients with definitive CP. sCD206 was also elevated in patients with definitive CP (p = 0.042). ROC analysis revealed that the optimal sCD163 cutpoint to distinguish definitive CP from controls was 1.84 mg/ml (AUC-ROC 0.65; 95 % confidence interval [CI], 0.54-0.77). The optimal sCD206 cutpoint to distinguish definitive CP from controls was 0.24 mg/ml (AUC-ROC 0.66; 95 % CI 0.54-0.78). The analytes did not significantly discriminate patients with suspected CP from controls. MCP-1 concentrations showed no differences across subgroups. Conclusion Our study demonstrates that subjects with definitive CP, sampled during a clinically quiescent phase, exhibited increased levels of sCD163 and sCD206. This indicates the presence of activated M2 macrophages in patients with CP at advanced, but not early, clinical stages.