Distinct immune characteristics distinguish hereditary and idiopathic chronic pancreatitis

Chronic pancreatitis (CP) is considered an irreversible fibroinflammatory pancreatic disease. Despite numerous animal model studies, questions remain about local immune characteristics in human CP. We profiled pancreatic immune cell characteristics in control organ donors and CP patients including those with hereditary and idiopathic CP undergoing total pancreatectomy with islet autotransplantation. Flow cytometric analysis revealed a significant increase in the frequency of CD68(+) macrophages in idiopathic CP. In contrast, hereditary CP samples showed a significant increase in CD3(+) T cell frequency, which prompted us to investigate the T cell receptor beta (TCR beta) repertoire in the CP and control groups. TCR beta sequencing revealed a significant increase in TCR beta repertoire diversity and reduced clonality in both CP groups versus controls. Interestingly, we observed differences in V beta-J beta gene family usage between hereditary and idiopathic CP and a positive correlation of TCR beta rearrangements with disease severity scores. Immunophenotyping analyses in hereditary and idiopathic CP pancreases indicate differences in innate and adaptive immune responses, which highlights differences in immunopathogenic mechanisms of disease among subtypes of CP. TCR repertoire analysis further suggests a role for specific T cell responses in hereditary versus idiopathic CP pathogenesis, providing insights into immune responses associated with human CP.