Circulating immune signatures in chronic pancreatitis with and without preceding acute pancreatitis: A pilot study

Abstract

Objective: To investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP).

Methods: We performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons of analytes were performed between the subgroups.

Results: In total, 133 patients with CP (111 with AP and 22 without AP) and 50 healthy controls were included. Among the 80 analytes studied, CP patients with a history of AP had significantly higher serum levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1 receptor antagonist, IL-15) and chemokines (Cutaneous T-Cell Attracting Chemokine (CTACK), Monokine induced Gamma Interferon (MIG), Macrophage-derived Chemokine (MDC), Monocyte Chemoattractant Protein-1 (MCP-1)) compared to CP without preceding AP and controls. In contrast, CP patients without AP had immune profiles characterized by low systemic inflammation and downregulation of anti-inflammatory mediators, including IL-10.

Conclusion: CP patients with a preceding history of AP have signs of systemic inflammatory activity even during a clinically quiescent phase. In contrast, CP patients without a history of AP have low systemic inflammatory activity. These findings suggest the presence of two immunologically diverse subtypes of CP.

Keywords: Chronic pancreatitis; Immune signatures.

Figure 1:

Volcano plot of differential Median Fluorescence Intensity (MFI) expressions between the total chronic pancreatitis (CP) population and controls. The dashed line represents the delineation between p-values less than 0.05 (above the line) and those greater than 0.05 (below the line). The x-axis indicates fold change, and the y-axis the statistical significance level of group differences in immune signature expressions.

Figure 2:

Volcano plot of differential Median Fluorescence Intensity (MFI) expressions between chronic pancreatitis (CP) population with preceding acute pancreatitis (AP) episode(s) and controls. The dashed line represents the delineation between p-values less than 0.05 (above the line) and those greater than 0.05 (below the line). The x-axis indicates fold change, and the y-axis the statistical significance level of group differences in immune signature expressions.

Figure 3:

Volcano Plot of differential Median Fluorescence Intensity (MFI) expressions between chronic pancreatitis (CP) population without preceding acute pancreatitis (AP) episode(s) and controls. The dashed line represents the delineation between p-values less than 0.05 (above the line) and those greater than 0.05 (below the line). The x-axis indicates fold change, and the y-axis the statistical significance level of group differences in immune signature expressions.

Figure 4:

Venn diagram of alterations in systemic immune markers in chronic pancreatitis (CP) with and without preceding acute pancreatitis (AP) episodes(s); healthy controls are used as the reference group.

Figure 5:

Volcano Plot of differential Median Fluorescence Intensity (MFI) expressions between chronic pancreatitis (CP) patients with and without previous acute pancreatitis (AP) episode(s). The dashed line represents the delineation between p-values less than 0.05 (above the line) and those greater than 0.05 (below the line). The x-axis indicates fold change, and the y-axis the statistical significance of the observed immune signatures.