Anti-zinc transporter protein 8 autoantibodies significantly improve the diagnostic approach to type 1 diabetes: an Italian multicentre study on paediatric patients

Abstract

Background and aim Anti-ZnT8 antibodies (ZnT8A) were recently proposed as a new independent serological marker in Type 1 diabetes (T1D), leading to a significant improvement of the positive predictive value of autoantibody measurement in this setting. The aim of this retrospective multicentre study was to investigate ZnT8A as a complement to the current T1D autoantibody assays in a large cohort of paediatric Italian patients.MethodsZnT8A were assessed by ELISA in 213 T1DM paediatric patients referred to six different centres in North-East Italy. Fifty-four were analysed at disease onset, 79 within 4 years from diagnosis and 80 after 5 or more years from diagnosis. Retrospective data about islet cell autoantibodies (ICA), anti-insulin (IAA), anti-glutamate decarboxylase (GADA) and anti-protein tyrosine phosphatase IA-2 (IA-2A) antibodies were collected and compared.ResultsOverall, ZnT8A showed positive results in 106/213 (49.8 %) T1D patients and were found in 10 (4.7 %) subjects previously classified as autoantibody negative based on the existing markers (GADA, IA-2A, IAA and ICA), increasing the overall diagnostic sensitivity from 85.9 to 90.6 %. ZnT8A disclosed the same sensitivity (61.1 %) at disease onset as GADA (61.1 %) and higher than IA-2A (53.7 %), with only GADA showing much persistence in the long-term follow-up. Focusing on patients at disease onset, all the ICA positive were associated with at least one positive autoantibody among GADA, IA-2A and ZnT8A, 16.7 % of whom presenting only anti-ZnT8-positive antibodies.ConclusionThis study confirms ZnT8A as an important additional and independent diagnostic marker of T1D and supports its introduction in the routine diagnostic process to replace less sensitive methods and improve the overall autoantibody sensitivity.Electronic supplementary materialThe online version of this article (doi:10.1007/s13317-015-0068-4) contains supplementary material, which is available to authorized users.

Zinc transporter 8 autoantibodies complement glutamic acid decarboxylase and insulinoma‐associated antigen‐2 autoantibodies in the identification and characterization of Japanese type 1 diabetes

“…Seeing as the incidence of type 1 diabetes in white people is much higher than in Japanese people, the frequency of incidental recruitment of anti‐islet autoantibody‐positive healthy individuals might also be higher in the white population. With this newly determined cut‐off value, the prevalence of ZnT8A in the 324 patients with type 1 diabetes was 24.7%, which was lower than in previous reports 6,14,15 . As the higher prevalence of ZnT8A in acute‐onset type 1 diabetic patients in comparison with the slowly progressive form observed in the present study was in accordance with previous reports, the possible reason for this discrepancy could be due to the differences in age, the duration of diabetes or the proportion of the subtype of type 1 diabetes 16 .…”

Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes

“…The discussion on the frequency and relation of ZnT8 Ab to diabetes features in open. In Italian multicentre study on paediatric patients it was proved, that ZnT8 Ab disclosed the same sensitivity (61%) at disease onset as GAD Ab (61%) [24]. Some authors prove almost 10% higher frequency of ZnT8 Ab compared to GAD Ab [25].…”

Autoantibodies in Diabetes Mellitus

“…Prevalence ZnT8A remained substantially stable in patients up to four years of clinical diagnosis, but then showed a significant decrease, and ZnT8A finally fixed at about 34% of 5 years-diagnosed patients. 43 The ZnT8A are appear between 60-80% of Caucasian patients with T1D at onset and together with IAA, GAD65, and IA-2A, can confirm the diagnosis of autoimmune diabetes in more 94% of subjects. Genetic risk in first-degree relatives T1D cases followed prospectively, ZnT8A appear at an average age of 3-4 years and generally persist until the onset of clinical disease.…”

“…ZnT8A associated with other autoantibodies, can improve diagnostic performance as a whole and a positive predictive value of laboratory. 43 When introducing ZnT8A as a complement of the current biomarker, the overall diagnostic performance significantly improved the serological test. The combination of GADA, IA-2A and ZnT8A as the most powerful and cost-effective diagnostic approach in patients with T1D.…”