Possible involvement of autoimmunity in fulminant type 1 diabetes

AbstractFulminant type 1 diabetes (FT1D) is characterized by a relatively low HbA1c level at the onset, despite the abrupt occurrence of marked hyperglycemia with ketosis or ketoacidosis. The initial symptoms/findings are flu-like, absence of islet-associated autoantibodies, and a drastic decrease in β-cells and α-cells, which strongly suggest the involvement of a viral infection. In fact, we successfully demonstrated that a FT1D-like phenotype can be reproduced in encephalomyocarditis virus-induced diabetes murine model. However, there is a discussion on the possible involvement of autoimmuni ty rather than viral infection as the underlying cause of FT1D. For example, HLA-DRB1*04:05, a susceptible antigen of type 1A diabetes, is reportedly associated with FT1D in Japan. Moreover, anti-glutamic acid decarboxylase antibody is reportedly detected in ~ 5% of the patients. Additionally, h alf of the patients with anti-programmed cell death-1 therapy-related type 1 diabetes fulfilled the criteria of the disease. These findings suggest that islet-associated autoimmunity can partially contribute to the development of FT1D. Furthermore, using nonobese diabetic mice with reduced regulator y T-cell (Treg) numbers, we found that a human FT1D-like phenotype can be induced by islet-associated autoimmunity through collaboration between innate immunity (macrophages and/or natural killer cells) and acquired immunity (predominantly cytotoxic CD8+ T cells) in genetically predisposed indi...
Source: Diabetology International - Category: Endocrinology Source Type: research