Unique Inflammatory Changes in Exocrine and Endocrine Pancreas in Enterovirus-induced Fulminant Type 1 Diabetes

Context: There is scant report on
the pathological changes of the exocrine and endocrine pancreas in fulminant
type 1 diabetes mellitus (FT1DM).

Objective: To clarify the distinct pathological changes in the exocrine
as well as the endocrine pancreas shortly after onset of the diabetes in FT1DM.

Method: The exocrine and endocrine pancreases of 3 FT1DM and 17 non-diabetic controls were immunohistochemically
examined for islet and exocrine tissue inflammation, infiltrating mononuclear
cell (MNC) CD subtype, enterovirus capsid protein 1 (VP1) localization, and CXC
chemokine ligand 10 (CXCL10) and CXC chemokine receptor 3 (CXCR3) expression.

Results: The median frequency of insulitis, observed in
all FT1DM pancreases, was 67%. In non-diabetic control pancreases, no insulitis
was observed. In the islets of FT1DM, the numbers of CD45+, CD3+, CD8+, CD68+
and CD11c+ MNCs were significantly higher than in the control group. In the
exocrine pancreas of FT1DM, the numbers of CD3+ T
cells, CD8+ T cells, CD68+ macrophages and CD11c+ dendritic cells were
significantly higher than in the control group. Infiltrating
CD8+ T cells, CD68+ macrophages and CD11c+ dendritic cells were observed around
exocrine acinar cells in FT1DM. VP1 and CXCL10 were detected in islet cells as
well as exocrine cells in FT1DM. CXCL10 positive exocrine cells were
surrounded by CXCR3+ T cells.

Conclusion: The pathological findings
suggested that suppression of activated CXCL10-CXCR3 axis in exocrine as well
as endocrine pancreas is a new therapeutic target in FT1DM and possibly in enter
virus associated acute-onset type1 diabetes.
Precis:This study reports the association between exocrine pancreas damage and enterovirus infection in fulminant type 1 diabetes(FT1DM).Importanat factors identified in the pancreas of FT1DM were enterovirus infection,inflammation involving chemokine/cytokine(CXCL10/CXCR3) network and apoptosis/necrosis of the pancreatic exocrine cells and islet cells.