IA-2 Autoantibodies

Type 1 diabetes, commonly referred to as insulin-dependent diabetes (IDDM), is caused by pancreatic beta-cell destruction that leads to an absolute insulin deficiency. The clinical onset of diabetes does not occur until 80% to 90% of these cells have been destroyed. Prior to clinical onset, type 1 diabetes is often characterized by circulating autoantibodies against a variety of islet cell antigens, including glutamic acid decarboxylase (GAD), tyrosine phosphatase (IA2), and insulin. The autoimmune destruction of the insulin-producing pancreatic beta cells is thought to be the primary cause of type 1 diabetes. The presence of these autoantibodies provides early evidence of autoimmune disease activity, and their measurement can be useful in assisting the physician with the prediction, diagnosis, and management of patients with diabetes. Autoantibodies to IA2, a tyrosine phosphatase-like protein, are found in 50% to 75% of type 1 diabetics at and prior to disease onset. These autoantibodies are generally more prevalent in younger onset patients. Because the risk of diabetes is increased with the presence of each additional autoantibody, the positive predictive value of the IA2 antibody test is enhanced when measured in conjunction with antibodies to GAD and insulin.

References:

Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997; 20(7):1183-1197. PubMed 9203460

Bonifacio E, Bingley PJ. Islet autoantibodies and their use in predicting insulin-dependent diabetes. Acta Diabetol. 1997 Oct; 34(3):185-193. PubMed 9401639

Verge CF, Gianani R, Kawasaki E, et al. Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes. 1996 Jul; 45(7):926-933. PubMed 8666144

Bingley PJ, Bonifacio E, Williams AJ, Genovese S, Bottazzo GF, Gale EA. Prediction of IDDM in the general population: Strategies based on combinations of autoantibody markers.Diabetes 1997 Nov; 46(11):1701-1710. PubMed 9356015

Pietropaolo M, Hutton JC, Eisenbarth GS, et al. Protein tyrosine phosphatase-like proteins: Link with IDDM. Diabetes Care. 1997 Feb; 20(2):208-214. PubMed 9118776

Pietropaolo M, Peakman M, Pietropaolo SL, et al. Combined analysis of GAD65 and ICA512(IA02) autoantibodies in organ and nonorgan-specific autoimmune diseases confers high specificity for insulin-dependent diabetes mellitus. J Autoimmun. 1998 Feb; 11(1):1-10. PubMed 9480718

Borg H, Fernlund P, Sundkvist G, et al. Protein tyrosine phosphatase-like protein IA2-antibodies plus glutamic acid decarboxylase 65 antibodies (GADA) indicates autoimmunity as frequently as islet cell antibodies assay in children with recently diagnosed diabetes mellitus. Clin Chem. 1997 Dec; 43(12):2358-2363. PubMed 9439455