Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes.

Summary, in English

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.

• Författare: C Andersson; Fariba Vaziri Sani; Aj Delli; Bengt Lindblad; Annelie Carlsson; G Forsander; J Ludvigsson; C Marcus; U Samuelsson; Sa Ivarsson; Åke Lernmark; H Elding Larsson
• Avdelning/ar: EXODIAB: Excellence of Diabetes Research in Sweden; Celiaki och diabetes; Pediatrik, Lund; Pediatrisk endokrinologi
• Publiceringsår: 2013
• Språk: Engelska
• Sidor: 97-105
• Publikation/Tidskrift/Serie: Pediatric Diabetes
• Volym: 14
• Issue: 2
• Länkar: http://dx.doi.org/10.1111/j.1399-5448.2012.00916.x
• Dokumenttyp: Artikel i tidskrift
• Förlag: Wiley-Blackwell
• Ämne: Endocrinology and Diabetes; Pediatrics
• Status: Published
• Projekt: Better Diabetes Diagnosis (BDD)
• Forskningsgrupp: Celiac Disease and Diabetes Unit; Paediatric Endocrinology
• ISBN/ISSN/Övrigt: ISSN: 1399-543X