Possible involvement of autoimmunity in fulminant type 1 diabetes
- PDF / 756,799 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 82 Downloads / 184 Views
MINI-REVIEW
Possible involvement of autoimmunity in fulminant type 1 diabetes Yoichi Oikawa1 · Akira Shimada1 Received: 10 August 2020 / Accepted: 17 August 2020 © The Japan Diabetes Society 2020
Abstract Fulminant 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 isletassociated 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 autoimmunity 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, half 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 regulatory 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 individuals of autoimmune type 1 diabetes with low Tregs or Treg dysfunction. To clarify greater details regarding the association of autoimmunity in the pathogenesis of FT1D, further studies using suitable animal models and accumulation of the relevant patients are required. Keywords Anti-glutamic acid decarboxylase antibody · CD28−/− nonobese diabetic mouse · Encephalomyocarditis virus · Fulminant type 1 diabetes · Polyinosinic-polycytidylic acid · Regulatory T cell
Introduction Fulminant type 1 diabetes (FT1D) is a novel subtype of type 1 diabetes and is characterized by a relatively low glycated hemoglobin (HbA1c) level at the onset, despite the abrupt occurrence of marked hyperglycemia with ketosis or ketoacidosis [1]. According to a nationwide survey of FT1D, ~ 72% of the patients with this diabetes have preceding flu-like symptoms, suggesting the involvement of viral infection in the development of the disease [2]. Moreover, 98% of the patients show increased levels of serum exocrine pancreatic enzymes, which is consistent with the reported findings of mononuclear infiltration in the exocrine pancreas [3]. * Yoichi Oikawa [email protected] 1
Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, 38 Morohongo, Moroyamamachi, Iruma‑gun, Saitama 350‑0495, Japan
Imagawa et al. initially reported that islet-assoc
Data Loading...
