Islet cell autoantibodies

Cell destruction during the development of IDDM is the result of autoimmune processes. Considerable evidence supports the autoimmune nature of IDDM. This evidence includes (1) observation of lymphocyte infiltration into pancreatic islets in biopsy specimens taken from patients in early stages of IDDM (2) the identification of islet-cell autoantibodies from patients with IDDM ... 

Diabetes mellitus type 1 (T1D). Autoimmune form of diabetes mellitus caused by immune-mediated destruction of insulin-producing beta cells in the pancreas with irreversible loss of insulin production. Islet cell autoantibodies and autoantibodies directed against glutamic acid decarboxylase, insulin, and the IA2-antigen are diagnostic markers for T1D as well as risk markers for the development of this disease. 

Rulli M, Kuusisto A, Salo J et al (1997) Time-resolved fluorescence imaging in islet cell autoantibody quantitation. J Immunol Methods 208 169-179... 

Circulating islet cell and p-cell specific autoantibodies are characteristic of prodromal periods of insulin-dependent diabetes mellitus. Conventional quantitation of these is often prone to errors because specific and unspecific fluorescence signals are difficult to separate. The situation can be dramatically improved if the Eu chelate [Eu(NTA-terpy)] conjugated to anti-human polyclonal IgG is used as the secondary antibody in a test of 57 patients, 96.5% were detected as being positive for islet cell autoantibodies compared to only 89.5% with the conventional test [105]. 

The pathogenesis of type I diabetes is autoimmune destruction of the cells of the pancreas. The factor or factors that trigger this autoimmune response are unknown. Predisposing factors appear to include certain major histocompatibility complex haplotypes and autoantibodies to various islet cell antigens. The progression of the autoimmune response is characterized by lymphocytic infiltration and destruction of the pancreatic cells resulting in insulin deficiency. Type I diabetes mellitus constitutes about 10% of cases of diabetes mellitus. 

Of 62 initially autoantibody-negative patients treated with interferon alfa for chronic hepatitis C for a mean of 8 months, three developed antibodies to 21b-hydroxylase, a sensitive assay of adrenocortical autoimmunity (528). However, there were no cases of Addison s disease or subclinical adrenal insufficiency. This study suggested that the adrenal cortex is another potential target organ of autoimmune effects of interferon alfa, along with thyroid and pancreatic islet cells. 

In patients with chronic hepatic B or C the respective prevalences of pancreatic autoantibodies increased from 2% and 3% at baseline to 5% and 7% after interferon (544). In all, 31 published cases of type 1 diabetes mellitus attributed to interferon alfa treatment were detailed, mostly in patients with hepatitis C. Irreversible diabetes required permanent insulin treatment in all but eight cases. At least one marker of pancreatic autoimmunity was positive in nine of 18 patients before treatment, and in 23 of 30 patients at the onset of diabetes. In accordance with these results and the likelihood of a genetic predisposition, the authors recommended screening for islet cell and glutamic acid decarboxylase autoantibodies before and during interferon alfa treatment. However, owing to the low number of reported cases and the paucity of studies that have examined the relation between pancreatic autoimmunity and the occurrence of diabetes, further research on the predictive potential of such a systematic investigation is warranted. 

Wesche B, Jaeckel E, Trautwein C, Wedemeyer H, Falorni A, Frank H, von zur Muhlen A, Manns MP, Brabant G. Induction of autoantibodies to the adrenal cortex and pancreatic islet cells by interferon alpha therapy for chronic hepatitis C. Gut 2001 48(3) 378-83. 

Qll There is both a genetic and environmental component in type 1 diabetes. The pathological basis of the condition is autoimmune destruction of the pancreatic islet cells, which is said to be associated with genetic and environmental factors such as viral infection. It has been shown that antibodies to islet cells and insulin autoantibody (IAA) can exist for years before the occurrence of symptoms, possibly as a result of the autoimmune processes the IAA may form during the process of active islet and /1-cell destruction. Both insulin and glucagon play a role in the development of hyperglycaemia and hyperketonaemia, since both a- and /1-cell functions are abnormal in diabetes. Both a lack of insulin and a relative excess of glucagon coexist in type 1 diabetes, and so the metabolic abnormalities that occur are likely to be caused by both hormones. 

Type-I diabetes is the result of an immunologically mediated genetically programmed destruction of the B-cells. This process may require many years and can be documented by several humoral and cellular immunological abnormalities preceding the clinical onset of the disease. Islet cell surface antibodies (ICA) and insulin autoantibodies (IAA) are often detected years before overt clinical symptoms start. A florid insulitis, however, has mainly been observed only close to the time of diagnosis (Bottazzo et al., 1985). 

Autoantibody markers of immune destruction are present in 85% to 90% of individuals with immune-mediated diabetes when fasting hyperglycemia is initially detected. Approximately 10% to 12% of white adult patients who have the type 2 diabetes phenotype also have islet cell auto antibodies, particularly to GADgs. This condition has been termed latent autoimmune diabetes of adulthood (LADA). Up to 1% to 2% of healthy individuals have a single autoantibody and are at low risk of developing immune-mediated diabetes. Because the prevalence of immune-mediated diabetes is low (-0.3% in the general... 

The NOD mouse strain is an excellent model of autoimmune disease and an important tool for dissecting tolerance mechanisms. The peculiarity of this mouse strain is that it develops spontaneous autoimmune diabetes, which shares many similarities to autoimmune or type la diabetes (TID) in humans, including the presence of pancreatic islet-specific autoantibodies, and autoreactive CD4 and CD8 T cells. 

Islet cell antibodies (ICA). Autoantibodies reacting with endocrine (pancreatic islet) cells and detectable by indirect immunofluorescence on pancreas cryostat sections. Diagnostic marker of diabetes mellitus type 1. 

Immunoisolation may also have an advantage in preventing the autoimmune destruction of the transplanted islets (27) by separating them from the host (T-cells or autoantibodies) by the permselective membrane. Although the detailed mechanism of islet cell damage is unknown, evidence from spontaneously diabetic BB rats indicates that the rapid failure of islet transplants, even in twins (28), may be due to a recurrence of autoimmune disease rather than the conventional transplant rejection phenomenon (29). 

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