Distinct immune characteristics distinguish hereditary and idiopathic chronic pancreatitis.
J Clin Invest
; 130(5): 2705-2711, 2020 05 01.
Article
em En
| MEDLINE
| ID: mdl-32053120
ABSTRACT
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 ß (TCRß) repertoire in the CP and control groups. TCRß sequencing revealed a significant increase in TCRß repertoire diversity and reduced clonality in both CP groups versus controls. Interestingly, we observed differences in Vß-Jß gene family usage between hereditary and idiopathic CP and a positive correlation of TCRß 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pancreatite Crônica
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos