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Zinc Transporter 8 (ZnT8) Antibody

Zinc Transporter 8 (ZnT8) Antibody

Test Summary

Zinc Transporter 8 (ZnT8) Antibody

  

Clinical Use

  • Confirm diagnosis of type 1 diabetes mellitus in symptomatic children and adults
  • Help predict development of type 1 diabetes mellitus in asymptomatic people at high risk

Clinical Background

Type 1 diabetes mellitus, which accounts for 5% to 10% of all diabetes cases,1 is characterized by destruction of insulin-producing pancreatic beta cells, hyperglycemia, ketoacidosis, and a need for exogenous insulin. Onset occurs most often in childhood but can happen at any age. Children typically present with hyperglycemia and/or ketoacidosis. Ketoacidosis is less frequent in people with adult onset. Compared to type 2 diabetes mellitus, adult-onset type 1 diabetes is associated with a leaner body mass, more rapid progression to insulin dependence, and a lower blood concentration of C-peptide.

Type 1 diabetes is associated with specific HLA DR and DQ haplotypes as well as development of one or more autoantibodies directed at the insulin-producing pancreatic beta cells.1 These autoantibodies include glutamic acid decarboxylase 65 (GAD-65) antibody, tyrosine phosphatase IA-2 (IA-2) antibody, insulin autoantibody (IAA), islet cell antibody (ICA), and zinc transporter 8 (ZnT8) antibody. Presence of 1 or more of these antibodies confirms the diagnosis of type 1 diabetes in symptomatic patients.1 In asymptomatic patients, presence of 1 or more of these antibodies may predict development of type 1 diabetes.1 The risk increases with increasing number and titer of antibodies and younger age at seroconversion.

ZnT8 antibody is the most recently discovered diabetes-related major autoantibody. Roughly 65% to 80% of children with recently diagnosed type 1 diabetes2,3 and 20% to 40% of adults with type 1 diabetes have antibodies to ZnT8.3-5 The exact percent varies among the different populations studied. ZnT8 antibody tests may be positive in 4% of children with a first-degree family history of type 1 diabetes.6 The antibody can be detected as early as 9 months of age but is more common after 2 years.2,6 Antibody titers decrease over the course of the disease, and patients who are initially ZnT8 antibody-positive may later become antibody-negative.3,7,8

Testing for the presence of ZnT8 antibody is important clinically for 2 reasons. First, ZnT8 antibody testing can help classify the type of diabetes and confirm an autoimmune etiology. When used in conjunction with tests for other autoantibodies (GAD-65, IA-2, and insulin), diagnostic sensitivity for type 1 diabetes is improved. This is because ZnT8 antibody occurs in 3% to 4% of patients with type 1 diabetes who are negative for these other 3 antibodies.2,7,9 Use of the 4 antibodies to diagnose patients results in 93% to 98% sensitivity.2,7,9

Second, ZnT8 antibody testing may help to assess the risk for type 1 diabetes. Achenbach et al found that almost half of children with ZnT8 antibody developed type 1 diabetes within 5 years.6 Moreover, since risk of type 1 diabetes increases with the number of antibodies, a positive ZnT8 antibody test can reclassify individuals into a higher risk category. However, the clinical value of predicting diabetes risk is limited. There is currently no therapy to prevent10 or slow the progression to disease onset. Still, more frequent monitoring may detect disease earlier, which may extend endogenous insulin production and limit development of complications.11

Individuals Suitable for Testing

  • Individuals with diabetes of uncertain etiology

    –  Young person with atypical diabetes

    –  Person with ketosis-prone diabetes that is not clearly type 1

    –  Person suspected of having maturity-onset diabetes of the young (MODY)

    –  Woman with gestational diabetes (help clarify risk of future diabetes)

  • Obese individual with acute-onset diabetes with ketoacidosis

  • Lean individuals with nonketotic diabetes
  • Individuals at high risk of developing type 1 diabetes (eg, those with a first-degree relative with type 1 diabetes) in context of a clinical research study1

Method

  • Enzyme-linked immunosorbent assay (ELISA)

  • Analytical specificity: 98% to 99% at type 1 diabetes onset7,9

  • Reportable range: 10-500 U/mL

Interpretive Information

ZnT8 antibody results above the reference range indicate an autoimmune etiology (ie, type 1 diabetes) in individuals with diagnosed diabetes. A result below the reference range, however, does not rule out type 1 diabetes. Testing for additional autoantibodies may be beneficial when type 1 diabetes is suspected.

In asymptomatic individuals, ZnT8 antibody results above the reference range may predict development of type 1 diabetes. A ZnT8 antibody result below the reference range does not rule out risk of type 1 diabetes, as other antibodies associated with risk of developing type 1 diabetes (GAD-65, IA-2, IAA, and ICA) may be present.1

References

  1. American Diabetes Association. Standards of medical care in diabetes—2017. Diabetes Care. 2017;40(suppl 1):S1-S120.

  2. Andersson C, Vaziri-Sani F, Delli A, et al. Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatr Diabetes. 2013;14:97-105.

  3. Vaziri-Sani F, Oak S, Radtke J, et al. ZnT8 autoantibody titers in type 1 diabetes patients decline rapidly after clinical onset. Autoimmunity. 2010;43:598-606.

  4. Kawasaki E, Nakamura K, Kuriya G, et al. Differences in the humoral autoreactivity to zinc transporter 8 between childhood- and adult-onset type 1 diabetes in Japanese patients. Clin Immunol. 2011;138:146-153.

  5. Hussein H, Ibrahim F, Sobngwi E, et al. Zinc transporter 8 autoantibodies assessment in daily practice. Clin Biochem. 2017;50:94-96.

  6. Achenbach P, Lampasona V, Landherr U, et al. Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk. Diabetologia. 2009;52:1881-1888.

  7. Petruzelkova L, Ananieva-Jordanova R, Vcelakova J, et al. The dynamic changes of zinc transporter 8 autoantibodies in Czech children from the onset of Type 1 diabetes mellitus. Diabet Med. 2014;31:165-171.

  8. Wenzlau JM, Walter M, Gardner TJ, et al. Kinetics of the post-onset decline in zinc transporter 8 autoantibodies in type 1 diabetic human subjects. J Clin Endocrinol Metab. 2010;95:4712-4719.

  9. Wenzlau JM, Moua O, Sarkar SA, et al. SlC30A8 is a major target of humoral autoimmunity in type 1 diabetes and a predictive marker in prediabetes. Ann N Y Acad Sci. 2008;1150:256-259.

  10. Ziegler AG, Rewers M, Simell O, et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013;309:2473-2479.

  11. Sørensen JS, Johannesen J, Pociot F, et al. Residual beta-cell function 3-6 years after onset of type 1 diabetes reduces risk of severe hypoglycemia in children and adolescents. Diabetes Care. 2013;36:3454-3459.
     

 Content reviewed 02/2017

 

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