[HTML][HTML] The diagnosis of insulitis in human type 1 diabetes

ML Campbell-Thompson, MA Atkinson, AE Butler… - Diabetologia, 2013 - Springer
ML Campbell-Thompson, MA Atkinson, AE Butler, NM Chapman, G Frisk, R Gianani…
Diabetologia, 2013Springer
Patients with insulitis are defined by the presence of a predominantly lymphocytic infiltration
specifically targeting the islets of Langerhans. The infiltrating cells may be found in the islet
periphery (peri-insulitis), often showing a characteristic tight focal aggregation at one pole of
the islet that is in direct contact with the peripheral islet cells. The infiltrate may also be
diffuse and present throughout the islet parenchyma (intra-insulitis). The lesion mainly
affects islets containing insulin-positive cells and is always accompanied by the presence of …
Patients with insulitis are defined by the presence of a predominantly lymphocytic infiltration specifically targeting the islets of Langerhans. The infiltrating cells may be found in the islet periphery (peri-insulitis), often showing a characteristic tight focal aggregation at one pole of the islet that is in direct contact with the peripheral islet cells. The infiltrate may also be diffuse and present throughout the islet parenchyma (intra-insulitis). The lesion mainly affects islets containing insulin-positive cells and is always accompanied by the presence of (pseudo) atrophic islets devoid of beta cells. The fraction of infiltrated islets is generally low (< 10% of islet profiles). The lesion should be established in a minimum of three islets, with a threshold level of≥ 15 CD45+ cells/islet before the diagnosis can be made. The pathology report should include the total number of islets analysed, the fraction of islets affected by insulitis, the fraction of (pseudo) atrophic islets, and a description of the spatial relationship of the infiltrate to the insulin-positive islet cells
Insulitis has, historically, been considered an inflammatory lesion of the islets of Langerhans, present in most children with recent-onset (< 1 year duration) type 1 diabetes as well as those subject to a rapid disease course [1, 2]. Together with the presence of circulating autoantibodies directed against islet cell antigens, the predominantly lymphocytic infiltrate has been regarded as strong evidence for an (auto) immune aetiology of the disease [3]. However, despite its presumed central role in beta cell destruction, the lesion is not well studied in patient material. Only 150–200 cases of insulitis have been described over the past century and very few of these cases have been analysed in depth and with current methodologies. In a recent meta-analysis it was found that 73% of children with recentonset (< 1 month duration) type 1 diabetes, between 0 and 14 years of age, showed insulitis compared with only 29% of 15–39 year-old recent-onset patients [4, 5]. In contrast to the robust lesion observed in the NOD mouse model, insulitis in type 1 diabetic patients is often mild with respect to both the number of infiltrating cells [6] and the fraction of islets showing infiltration (< 10%)[4]. In addition, residual insulinpositive islets remain present in a majority of type 1 diabetic patients, even up to 50 years following diagnosis [7–9]. One of the primary, if not the most difficult, challenges to our understanding of the pathogenesis of type 1 diabetes is the comparison between histopathological studies of type 1 diabetic patients, a facet complicated by the lack of a consensus definition of insulitis. Indeed, not only are there multiple differences between the immunophenotyping markers that are used to
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