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Semin Immunopathol (2014) 36:569579 DOI 10.1007/s00281-014-0438-4
REVIEW
Insulitis in human type 1 diabetes: a comparison between patients and animal models
Peter Int Veld
Received: 31 January 2014 /Accepted: 24 June 2014 /Published online: 9 July 2014 # The Author(s) 2014. This article is published with open access at Springerlink.com
Abstract Human type 1 diabetes (T1D) is considered to be an autoimmune disease, with CD8+ T-cell-mediated cytotoxicity being directed against the insulin-producing beta cells, leading to a gradual decrease in beta cell mass and the development of chronic hyperglycemia. The histopathologically defining lesion in recent-onset T1D patients is insulitis, a relatively subtle leucocytic infiltration present in approximately 10 % of the islets of Langerhans from children with recent-onset (<1 year) disease. Due to the transient nature of the infiltrate, its heterogeneous distribution in the pancreas and the nature of the patient population, material for research is extremely rare and limited to a cumulative total of approximately 150 cases collected over the past century. Most studies on the etiopathogenesis of T1D have therefore focused on the nonobese diabetic (NOD) mouse model, which shares many genetic and immunological disease characteristics with human T1D, although its islet histopathology is remarkably different. In view of these differences and in view of the limited success of clinical immune interventions based on observations in the NOD mouse, there is a renewed focus on studying the path-ogenetic process in patient material.
Keywords Autoimmunity . Insulin . Insulitis . Islets of
Langerhans . Pancreas . Type 1 diabetes
Human type 1 diabetes
Type 1 diabetes (T1D) is a chronic (auto)immune disease that causes a specific destruction of most insulin-producing
pancreatic beta cells, leading to overt hyperglycemia, a need for lifelong exogenous insulin replacement therapy and a high risk for developing debilitating chronic complications. Although the disease can occur at any age, there is a peak in newly diagnosed cases between 5 and 7 years of age and at or near puberty. In contrast to other autoimmune diseases, where there is a clear female preponderance, slightly more males develop T1D than females. The incidence shows geographical variability, ranging between 0.1 and 60 cases per 100,000 people, but its true level is difficult to ascertain as the disease is probably under-diagnosed, with many T2D patients...