title: Anti-zinc transporter protein 8 autoantibodies significantly improve the diagnostic approach to type 1 diabetes: an Italian multicentre study on paediatric patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  ZnT8A 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.
  
  
  RESULTS
  Overall, 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Institute of Clinical Pathology, University Hospital of Udine, Piazzale S. Maria Misericordia 15, 33100, Udine, Italy, fabris.martina@aoud.sanita.fvg.it.
authors.forename: Martina
authors.initials: M
authors.lastname: Fabris
authors.forename: Silvia
authors.initials: S
authors.lastname: Zago
authors.forename: Marco
authors.initials: M
authors.lastname: Liguori
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Trevisan
authors.forename: Manuela
authors.initials: M
authors.lastname: Zanatta
authors.forename: Alberto
authors.initials: A
authors.lastname: Comici
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zanette
authors.forename: Eva
authors.initials: E
authors.lastname: Carlin
authors.forename: Francesco
authors.initials: F
authors.lastname: Curcio
authors.forename: Elio
authors.initials: E
authors.lastname: Tonutti