Anti Islet Cell Antibodies

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1. What is islet cell antibody test?

Islet autoantibody testing is mainly used to help distinguish type 1 diabetes from diabetes due to other causes. Islet autoantibodies are positive in type 1 diabetes and are negative in diabetes cases which are caused by non-autoimmune problems.

2. Other than Diabetes in which conditions are islet cell antibody detected?

Islet autoantibodies may also be seen in patients with other autoimmune endocrine disorders such as Hashimoto thyroiditis or autoimmune Addison disease. Such individuals are found to be at an increased risk to develop type 1 diabetes.

3. Can the test be used to diagnose diabetes?

No. Type 1 diabetes as well as other types of diabetes are screened for, diagnosed, and monitored using tests for blood glucose and/or Hb A1c. The autoantibody tests can be used after diabetes is already diagnosed to help differentiate between type 1 and type 2 diabetes.

4. What is the significance of islet cell antibody test in research studies?

Testing non-diabetic individuals for islet autoantibodies is recommended only as part of a research study. In research settings, these islet autoantibody tests may be used to help predict the development of type 1 diabetes in family members of those who are affected. In general, the more islet autoantibodies that a non-diabetic person has in their blood, the higher is their risk for later developing type 1 diabetes. If a non-diabetic individual with one or more islet autoantibodies also has a low insulin response to the intravenous injection of glucose, their risk for type 1 diabetes can be high. More specifically, in first degree relatives of people with type 1 diabetes who have ICA and a low insulin response to intravenous injection of glucose, the risk of developing type 1 diabetes within 5 years is more than 50%. GADA has a similar predictive power. People with multiple islet autoantibodies can have a 10-year risk for developing type 1 diabetes that approaches 100%.

5. Do the autoantibodies ICA, IAA,GADA,GAD65,ZnT8A,IA-2A destroy the beta cells?

They are associated with beta cell destruction and reflect an ongoing autoimmune process, but they are not thought to cause the damage.

6. Does the early detection of beta cell destruction result in its prevention?

Not at present. The presence of islet autoantibodies indicates the cause of the diabetes but does not indicate if the patient has diabetes or does not have diabetes. There is debate if islet autoantibody screening should be performed at all even if we cannot prevent type 1 diabetes. This is because (even now) around 30% of children with new-onset type 1 diabetes have diabetic ketoacidosis (DKA), which can be fatal in approximately 1 in 200 children. If we screened for islet autoantibodies and asked patients and parents to be vigilant for the development of diabetes symptoms, theoretically DKA should be preventable at onset.

7. What is the methodology for the antibody test?

Semi-Quantitative Indirect Fluorescent Antibody.

8. What are Islet autoantibodies?

Islet autoantibodies are markers which appear when insulin producing beta cells in pancreas are damaged. They can be detected a long time before beta cells are completely destroyed. The autoantibodies are used to estimate a patient’s risk of developing type 1diabetes. This information can be used to select people who are potentially eligible to take part in clinical trials which test potential treatments that might delay or prevent type 1 diabetes. Islet autoantibody testing can also to help clinicians to classify the type of diabetes and decide on the best treatment in people in whom this is not clear. The first islet autoantibodies which were to be discovered were those that bound to the islet cells of human pancreas. The islet autoantibodies which are currently measured bind to: Glutamic acid decarboxylase65 (GAD),Protein tyrosine phosphatase islet antigen-2 (IA2),Insulin and Zinc transporter 8 (ZnT8).

9What is the sequence of antibody development?

Islet autoantibodies most commonly appear in a particular sequence, with insulin or GAD autoantibodies developing first, sometimes as early as 6 months of age, to be followed by IA2 and ZnT8 autoantibodies. This spreading of autoimmunity to different islet proteins do indicate that the process leading to destruction of the insulin producing cells is progressing. Further,the progression is also marked by the development of antibodies that recognize different regions of the target islet proteins.

9. What is the relationship between the autoantibodies that a person develops and their diabetes susceptibility genes. ?

According to literature, people with HLA DRB1*04 alleles have increased levels of IA2 autoantibodies at the time of diagnosis of type 1 diabetes. It is found that patients with HLA DRB1*09 alleles were also more likely to develop IA-2 autoantibodies. It is also found that IA2 autoantibody development was increased in patients carrying the neutral risk HLA DRB1*07 allele 

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