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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Figure1

Association of ZnT8A with GADA and IA-2A in 539 T1D patients. (A) Venn diagram of autoantibody combinations in autoantibody positive patients with T1D; (B) Correlation between ZnT8A and IA-2A index (non-parametric Spearman correlation coefficient R=0.222, P=0.000).

Figure 2

Prevalence of ZnT8A in T1D patients relation to age at diagnosis (A) and BMI (B); Data are expressed as n (%); (A)When compared with age at diagnosis >40yr, *P<0.05; (B) When compared with BMI>25.0kg/m², *P<0.05, **P<0.01.