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

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.

MATERIALS AND 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) compared to suspected CP. ROC analysis revealed 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). 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.