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.
BACKGROUND:Zinc transporter-8 (ZnT8) was recently identified as a novel autoantigen in humantype 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 humanZnT8 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.
Authors: E Kawasaki; M Uga; K Nakamura; G Kuriya; T Satoh; K Fujishima; M Ozaki; N Abiru; H Yamasaki; J M Wenzlau; H W Davidson; J C Hutton; K Eguchi Journal: Diabetologia Date: 2008-10-11 Impact factor: 10.122
Authors: J De Grijse; M Asanghanwa; B Nouthe; N Albrecher; P Goubert; I Vermeulen; S Van Der Meeren; K Decochez; I Weets; B Keymeulen; V Lampasona; J Wenzlau; J C Hutton; D Pipeleers; F K Gorus Journal: Diabetologia Date: 2009-11-29 Impact factor: 10.122
Authors: J S Petersen; K R Hejnaes; A Moody; A E Karlsen; M O Marshall; M Høier-Madsen; E Boel; B K Michelsen; T Dyrberg Journal: Diabetes Date: 1994-03 Impact factor: 9.461
Authors: Janet M Wenzlau; Kirstine Juhl; Liping Yu; Ong Moua; Suparna A Sarkar; Peter Gottlieb; Marian Rewers; George S Eisenbarth; Jan Jensen; Howard W Davidson; John C Hutton Journal: Proc Natl Acad Sci U S A Date: 2007-10-17 Impact factor: 11.205
Authors: Chi Zhang; Zhi-Guang Zhou; Jian Lin; Gan Huang; Jian-Ping Wang; Dong-Mei Zhang; Min Zhou; Xiao-Lin Yang Journal: Zhonghua Yi Xue Za Zhi Date: 2008-03-25
Authors: Tamara J Nicolson; Elisa A Bellomo; Nadeeja Wijesekara; Merewyn K Loder; Jocelyn M Baldwin; Armen V Gyulkhandanyan; Vasilij Koshkin; Andrei I Tarasov; Raffaella Carzaniga; Katrin Kronenberger; Tarvinder K Taneja; Gabriela da Silva Xavier; Sarah Libert; Philippe Froguel; Raphael Scharfmann; Volodymir Stetsyuk; Philippe Ravassard; Helen Parker; Fiona M Gribble; Frank Reimann; Robert Sladek; Stephen J Hughes; Paul R V Johnson; Myriam Masseboeuf; Remy Burcelin; Stephen A Baldwin; Ming Liu; Roberto Lara-Lemus; Peter Arvan; Frans C Schuit; Michael B Wheeler; Fabrice Chimienti; Guy A Rutter Journal: Diabetes Date: 2009-06-19 Impact factor: 9.461
Authors: Vito Lampasona; Antonio Petrone; Claudio Tiberti; Marco Capizzi; Marialuisa Spoletini; Sergio di Pietro; Marco Songini; Sara Bonicchio; Francesco Giorgino; Ezio Bonifacio; Emanuele Bosi; Raffaella Buzzetti Journal: Diabetes Care Date: 2009-10-06 Impact factor: 19.112