Article

The diagnostic value of zinc transporter 8 autoantibody (ZnT8A) for type 1 diabetes in Chinese

Diabetes Center, Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, China.
Diabetes/Metabolism Research and Reviews (Impact Factor: 3.59). 10/2010; 26(7):579-84. DOI: 10.1002/dmrr.1128
Source: PubMed

ABSTRACT Zinc transporter-8 (ZnT8) was recently identified as a novel autoantigen in human type 1 diabetes (T1D). Autoantibody to ZnT8 (ZnT8A) was detected in up to 80% of patients with new-onset T1D and 26% of patients with T1D otherwise classified as negative on the basis of existing markers. As no data of ZnT8A in Chinese have been reported, we aim to evaluate the utility of ZnT8A for diagnosis of autoimmune T1D in Chinese relative to other autoantibody markers.
Radioligand binding assays were performed on 539 T1D sera using human ZnT8 carboxyterminal 325Arg construct or a dimer incorporating 325Arg and 325Trp alongside antibodies to glutamic acid decarboxylase (GADA) or insulinoma-associated protein 2 (IA-2A). The antigenic specificity was analysed in the context of clinical characteristics of the patients.
ZnT8A were present in 24.1% (130 of 539) of patients with T1D versus 1.8% (10 of 555; P < 0.001) in type 2 diabetes. At diagnosis, ZnT8A and IA-2A were less prevalent in Chinese subjects with T1D than in Caucasian populations (both P < 0.001) but similar to Japanese. The diagnostic sensitivity of combined GADA, IA-2A and ZnT8A measurements reached 65.5% with ZnT8A detected in 13.5% (29 of 215) of GADA and/or IA-2A-negative subjects. ZnT8A prevalence was lower in older and fatter patients. ZnT8A+ alone patients were distinguished from Ab- ones (P < 0.05-0.001) on the basis of higher insulin requirement and lower systolic blood pressure level.
ZnT8A is an independent marker for T1D in Chinese and combined with GADA and IA-2A enhances diagnostic sensitivity. ZnT8A may be associated with different clinical phenotypes than GADA or IA-2A.

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    • "Serum was analyzed for the presence of GAD-Ab by highly sensitive and specific quantitative radioligand binding assay methods as reported previously [12]. Intra-assay and inter-assay coefficients of variation were 8.9% and 11.2% (n=5) respectively. "
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    • "It has been recently defined as a major target of humoral autoimmunity in human T1D based on a bioinformatics analysis (Dang et al., 2011; Wenzlau et al., 2009). Autoantibodies to ZnT8 (ZnT8A) have been therefore detected in high prevalence in newly diagnosed type 1 diabetic patients (Yang et al., 2010) and obviously overlap with GADA, IA2A, and IAA (Wenzlau et al., 2007). Of note, ZnT8 autoimmunity could be an independent marker of T1D, given that ZnT8As can be present in antibody-negative individuals and in type 2 diabetes, and in patients with other autoimmune disorders (Wenzlau et al., 2008). "
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    The Journal of Clinical Endocrinology and Metabolism 01/2012; 97(1):E54-8. DOI:10.1210/jc.2011-1930 · 6.31 Impact Factor
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