Supplemental digital content is available in the text.

No abstract

Context There are scant reports 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 diabetes in FT1DM. Design The exocrine and endocrine pancreases of 3 patients with FT1DM and 17 nondiabetic 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) expressions. Results The median frequency of insulitis in the 3 FT1DM pancreases was 60%. In the nondiabetic 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 those of 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 those of the control group. Infiltrating CD8+ T cells, CD68+ macrophages, and CD11c+ dendritic cells were observed around exocrine acinar cells in FT1DM. There was a close association between VP1 and CXCL10 expression in pancreatic exocrine ductal cells and acinar cells as well as islet cells in FT1DM. CXCL10+ exocrine cells were surrounded by CXCR3+ T cells. Conclusion The pathological findings suggested that suppression of the activated CXCL10–CXCR3 axis in the exocrine as well as the endocrine pancreas is a novel therapeutic target in FT1DM and possibly in enterovirus-associated acute-onset type 1 diabetes.

No abstract

Aims/Introduction: The need for antiserum for immunohistochemical (IHC) detection of enterovirus (EV) in formaldehyde-fixed and paraffin-embedded samples is increasing. The gold standard monoclonal antibody (clone 5D8/1) against EV-envelope protein (VP1) was proven to cross-react with other proteins. Another candidate marker of EV proteins is 2A protease (2A pro ), which is encoded by the EV gene and translated by the host cells during EV replication, and participates processing proproteins to viral capsid proteins. Materials and Methods: We raised polyclonal antiserum by immunizing a rabbit with an 18-mer peptide of Coxsackievirus B1 (CVB1)-2A pro , and examined the specificity and sensitivity for EV on formaldehyde-fixed and paraffin-embedded tissue samples. Results: Enzyme-linked immunosorbent assay study showed a high titer of antibody for 18-mer peptide of CVB1-2A pro , cross-reacting with CVB3-2A pro peptide. IHC showed that antiserum against 2A pro reacted with CVB1-infected and VP1-positive Vero cells. Confocal laser scanning microscopy showed that antigen stained by the 2A pro antibody located in the same cell with VP1 stained by 5D8/1. IHC using 2A pro antiserum showed dense staining in the islets of EV-associated fulminant type 1 diabetes pancreas and that located in the same cell stained positive for VP1 (5D8/1). Specificity of 2A pro antiserum by IHC staining was confirmed by negative 2A pro in 14 VP1-negative non-diabetes control pancreases. Conclusions: Our study provides a new polyclonal antiserum against CVB1-2A pro , which might be useful for IHC of EV-infected human tissues stored as archive of formaldehyde-fixed and paraffin-embedded tissue samples.