Islet-Cell-Surface Antibodies in Juvenile Diabetes Mellitus

Abstract

Using an indirect immunofluorescence test on suspensions of viable, insulin-producing islet cells from rats, we found that 32 per cent (28/88) of insulin-treated patients with juvenile diabetes have islet-cell-surface antibodies in their circulation. These antibodies also occurred in four of nine children with glucose intolerance, in one of 24 healthy children and in nondiabetic children with thyroid disorders. In the diabetic children, the immunofluorescent reaction was inhibited by preadsorption of serum to islet cells but was little affected by preadsorption to rat hepatocytes or erythrocytes or to acetone powders of various rat tissues, including pancreas. These results show that organ-specific, nonspecies-specific antibodies reactive with the cell surface of the islet cells can be present in serum from diabetic children, and provide an approach to investigation of immunopathological aspects of diabetes mellitus.

The biosociology of pancreatic B cells

“…These IgG antibodies were primarily detected in recently diagnosed Type 1 (insulin-dependent) diabetic patients younger than 30 years of age [27], the population wherein ICSA were first described [28]. They have been used to fluorescently label the islet B cells so that they become separable by fluorescence-activated cell sorting [27].…”

Increased GABAA channel subunits expression in CD8+ but not in CD4+ T cells in BB rats developing diabetes compared to their congenic littermates

“…A unique feature of the BB rat is that lymphophenia is a prerequisite for diabetes (Markholst et al, 1991) in addition to cells of the immune system that are thought to be actively involved in the destruction of the pancreatic islet  cells (Ramanathan and Poussier, 2001). Glutamic acid decarboxylase (GAD), which catalyses the formation of GABA from glutamate is a major autoantigen in type 1 diabetes (Lernmark et al, 1978). The signal molecule GABA binds to GABA A receptors (GABA A channels) and opens their chloride channel.…”

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

“…An immunological pathogenesis for Type 1 (insulin-dependent) diabetes mellitus is supported by the presence of inflammatory cells in the islets of Langerhans at onset [1][2][3] and of autoantibodies, reacting with pancreatic islet cells [4][5][6], insulin [7], or a Beta-cell Mr 64,000 (64K) protein [8], as early as several years prior to clinical onset [9][10][11][12].…”