Islet Antigen 2 (IA-2) Antibody, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Islet cell autoantibodies have been known to be associated with type 1 diabetes mellitus for 36 years. In recent years, several autoantigens against which islet antibodies are directed have been identified. These include the tyrosine phosphatase-related islet antigen 2 (IA-2), glutamic acid decarboxylase 65, the zinc transporter ZnT8, and insulin. One or more of these autoantibodies are detected in 96% of patients with type 1 diabetes, and are detectable before clinical onset, as well as in symptomatic individuals. A serological study of 50 type 1 diabetics and 50 control subjects conducted simultaneously across 43 laboratories in 16 countries demonstrated a median sensitivity of 57% and a median specificity of 99% for IA-2 antibody in type 1 diabetes. Prospective studies in relatives of patients with type 1 diabetes have shown that development of 1 or more islet autoantibodies (including IA-2 antibody) provides an early marker of progression to type 1 diabetes. Autoantibody profiles identifying patients destined to develop type 1 diabetes are usually detectable before age 3. In 1 study of relatives seropositive for IA-2 antibody, the risk of developing type 1 diabetes within 5 years was 65.3%. Some patients with type 1 diabetes are initially diagnosed as having type 2 diabetes because of symptom onset in adulthood, societal obesity, and initial insulin-independence. These patients with "latent autoimmune diabetes in adulthood" may be distinguished from those patients with type 2 diabetes by detection of 1 or more islet autoantibodies (including IA-2).
Clinical distinction of type 1 from type 2 diabetes mellitus
Identification of individuals at risk of type 1 diabetes (including high-risk relatives of patients with diabetes)
Prediction of future need for insulin treatment in adult-onset diabetic patients
Seropositivity for IA-2 autoantibody (> 0.02 nmol/L) is supportive of:
-A diagnosis of type 1 diabetes
-A high risk for future development of diabetes
-A current or future need for insulin therapy in patients with diabetes
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Negative results do not exclude the diagnosis of or future risk for type 1 diabetes mellitus. The risk of developing type 1 diabetes may be stratified further by testing for: 1) antibodies targeting insulin, glutamic acid decarboxylase, and zinc transporter 8 (ZnT8) and 2) HLA genetic markers. Careful monitoring of hyperglycemia is the mainstay of determining the requirement for insulin therapy.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
< or =0.02 nmol/L
Reference values apply to all ages.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Bingley PJ: Clinical applications of diabetes antibody testing. J Clin Endocrinol Metab 2010;95:25-33
2. Bingley PJ, Bonifacio E, Mueller PW: Diabetes Antibody Standardization Program: first assay proficiency evaluation. Diabetes 2003;52:1128-1136
3. Christie MR, Roll U, Payton MA, et al: Validity of screening for individuals at risk for type I diabetes by combined analysis of antibodies to recombinant proteins. Diabetes Care 1997;20:965-970
4. Lampasona V, Petrone A, Tiberti C, et al: Zinc transporter 8 antibodies complement GAD and IA-2 antibodies in the identification and characterization of adult-onset autoimmune diabetes: Non Insulin Requiring Autoimmune Diabetes (NIRAD) 4. Diabetes Care 2010;33:104-108