Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes.
Summary of "Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes."
OBJECTIVE:
To establish the diagnostic sensitivity of and the relationships between autoantibodies to all three Zinc transporter 8 (Zinc transporter 8 autoantibody to either one, two, or all three amino acid variants at position 325, ZnT8A) variants to human leukocyte antigen (HLA)-DQ and to autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A), and insulin (IAA).
METHODS:
We analyzed 3165 patients with type 1 diabetes (T1D) in the Better Diabetes Diagnosis study for HLA-DQ genotypes and all six autoantibodies (ZnT8RA, arginine 325 Zinc transporter 8 autoantibody; ZnT8WA, tryptophan 325 Zinc transporter 8 autoantibody; ZnT8QA, glutamine 325 Zinc transporter 8 autoantibody; GADA, IA-2A, and IAA).
RESULTS:
ZnT8A was found in 65% of the patients and as many as 108 of 3165 (3.4%) had 1-3 ZnT8A alone. None had ZnT8QA alone. Together with GADA (56%), IA-2A (73%), and IAA (33%), 93% of the T1D patients were autoantibody positive. All three ZnT8A were less frequent in children below 2 yr of age (p < 0.0001). All three ZnT8A were associated with DQA1-B1*X-0604 (DQ6.4) and DQA1-B1*03-0302 (DQ8). ZnT8WA and ZnT8QA were negatively associated with DQA1-B1*05-02 (DQ2).
CONCLUSIONS:
Analysis of ZnT8A increased the diagnostic sensitivity of islet autoantibodies for T1D as only 7% remained islet autoantibody negative. The association between DQ6.4 and all three ZnT8A may be related to ZnT8 antigen presentation by the DQ6.4 heterodimer.
Affiliation
Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmö, Sweden.
Journal Details
This article was published in the following journal.
Name: Pediatric diabetes
ISSN: 1399-5448
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22957668
- DOI: http://dx.doi.org/10.1111/j.1399-5448.2012.00916.x
Medical and Biotech [MESH] Definitions
Immunoglobulins, Thyroid-stimulating
Autoantibodies that bind to the thyroid-stimulating hormone (TSH) receptor (RECEPTORS, THYROTROPIN) on thyroid epithelial cells. The autoantibodies mimic TSH causing an unregulated production of thyroid hormones characteristic of GRAVES DISEASE.
Graves Disease
A common form of hyperthyroidism with a diffuse hyperplastic GOITER. It is an autoimmune disorder that produces antibodies against the THYROID STIMULATING HORMONE RECEPTOR. These autoantibodies activate the TSH receptor, thereby stimulating the THYROID GLAND and hypersecretion of THYROID HORMONES. These autoantibodies can also affect the eyes (GRAVES OPHTHALMOPATHY) and the skin (Graves dermopathy).
Autoantibodies
Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.
Autoantigens
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Hepatitis, Autoimmune
A chronic self-perpetuating hepatocellular INFLAMMATION of unknown cause, usually with HYPERGAMMAGLOBULINEMIA and serum AUTOANTIBODIES.
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