Detection and characterization of ZnT8 autoantibodies could help to screen latent autoimmune diabetes in adults-onset patients with type 2 phenotype

TRABUCCHI, ALDANA; FACCINETTI, NATALIA I.; GUERRA, LUCIANO L.; PUCHULU, FÉLIX M.; FRECHTEL, GUSTAVO D.; POSKUS, EDGARDO; VALDEZ, SILVINA N.

AUTOIMMUNITY

TAYLOR & FRANCIS LTD

Lugar: Londres; Año: 2012 vol. 45 p. 137 - 142

0891-6934

Autoantibodies to zinc transporter 8 (ZnT8A) constitute an additional marker of autoimmune diabetes, complementing thosealready used in diagnosis support. ZnT8A could also be found in latent autoimmune diabetes of adults (LADA). The aimof this study was to evaluate the prevalence of ZnT8A in adult-onset diabetic patients in Argentinian population. A total of271 patients diagnosed for diabetes at mean age 53.4 ^ 10.9, body mass index #30, without insulin treatment for thefirst year of disease, and initially classified as type 2 diabetic patients were tested for ZnT8A using cDNA plasmids encodingthe C-terminal domains (aa 268?369) carrying 325Arg, 325Trp, and a dimeric cDNA construct carrying both 325Arg and325Trp (ZnT8 Arg?Trp325).We also analyzed proinsulin autoantibodies (PAA), glutamic acid decarboxylase autoantibodies(GADA), and protein tyrosine phosphatase IA-2 autoantibodies (IA-2A). A subset of 101 patients was followed during 6 yearsin order to analyze insulin requirement. Out of the 271 patients, 22.1% presented at least one humoral marker, 2.6%were PAA þ , 12.5% were GADA þ , 3.3% were IA-2A þ , and 10.7% were ZnT8A þ . Among the latter, 7.0% wereZnT8A?Arg325, 51.7% were ZnT8A?Trp325, and 62.1% were ZnT8A?Arg?Trp325. Furthermore, the prevalence ofautoantibodies in the group of patients treated with insulin (n ¼ 18) was 55.6%. These results demonstrated that a significantproportion of autoimmune adult-onset diabetic patients presented ZnT8A as the only humoral marker. Between them,the higher prevalence was for ZnT8A?Trp325.We suggest that screening for LADA patients, best performed with a minimalset of marker determination, must include at least the screening of GADA and ZnT8A?Arg?Trp325.