Circumstantial evidence has implicated enteroviral infection in the etiology of type 1 diabetes but direct support for the hypothesis has been difficult to obtain. In order to verify the presence of enteroviruses in the pancreas, we analyzed pancreatic VP1 immunopositivity and MHC-I expression in both the exocrine and endocrine areas of pancreas samples from T1D patients, autoantibody positive individuals and healthy controls.
Materials and Methods
Serial sections from control, T1D and autoantibody positive (AAb+) cases were prepared by the nPOD Pathology Core and distributed to nPOD-V consortium laboratories. Samples were immunostained and quantified for enteroviral capsid protein (IHC) and class I MHC (using IHC in FFPE (UK) sections and IF (USA) in frozen sections). Enterovirus was searched for in frozen spleen samples.
Concordance between the level of MHC-I expression assessed by IHC and IF was very high. All nPOD controls were judged to display normal MHC-I expression in both laboratories (UK and USA). Most of the AAb+ cases also had normal MHC-I expression in the islets but, surprisingly, 5 of 9 exhibited higher MHC-I expression within regions of the exocrine pancreas. Importantly, this correlated with detection of occasional VP1+ exocrine cells. All 13 T1D cases with insulin-containing islets, hyper-expressed MHC-I and had islet VP1 immunopositivity. Several T1D cases also displayed elevated MHC-I and VP1 staining in the exocrine compartment. To extend this work, spleen samples from a small proportion of cases in which VP1 immunopositivity was found, were used tested by virus culture and gene amplicfication. Enterovirus genomes were detected.
A high proportion of T1D and AAb+ patients present MHC-I hyper-expression either in islets and/or in regions of the exocrine pancreas and this correlates with immunodetection of enteroviral VP1. The data imply that enteroviral infection is associated with abnormal pancreatic expression of MHC-I, a characteristic feature of T1D.