Characterization of Zinc Transporter 8 antibodies in autoimmune diabetic patients from Argentinian population using monomeric, homodimeric and heterodimeric ZnT8 antigen variants.

GUERRA, LUCIANO L.; FRECHTEL, GUSTAVO D.; TRABUCCHI, ALDANA; FACCINETTI, NATALIA I.; IACONO, RUBEN F.; PENAS STEINHARDT, ALBERTO; POSKUS, EDGARDO; TRIFONE LILIANA; VALDEZ, SILVINA N.

EUROPEAN JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2016 vol. 174 p. 157 - 165

0804-4643

The aim of this study was to characterize in depth ZnT8 autoantibodies (ZnT8A) by using alternative polymorphic monomeric and artificial dimeric polypeptides on the two major groups comprising autoimmune Diabetes Mellitus (DM): new-onset type 1 and non-obese adult-onset diabetic patients.One hundred sera from type 1 Argentinian diabetic patients and 282 subjects diagnosed with DM at the age of >30 years and body mass index ≤30, were tested for ZnT8A. The antigens employed were obtained using cDNA plasmids encoding the C-terminal domain of ZnT8 carrying 325Arg or 325Trp, and 3 dimeric constructs (ZnT8-Arg-Trp325, ZnT8-Arg-Arg325 and ZnT8-Trp-Trp325). Other routine beta-cell autoantibodies were also tested.Among type 1 diabetic patients, the whole prevalence of ZnT8A was 65.0%. Fifty six percent of them had autoantibodies against the ZnT8-Arg-Trp325 heterodimeric construct, whereas the other variants were recognized with circa 42% of positivity. On the other hand, the 282 non-obese adult-onset diabetic patients exhibited a different profile against the same set of antigens: the whole prevalence of ZnT8A was 16.3%, while 8.2% had autoantibodies against ZnT8-Arg-Arg325 and 6.4% against ZnT8-Arg-Trp325.An increased detection of humoral autoimmunity was found in both groups when ZnT8A was employed in combination with the conventional triad. Besides, exclusive reactivity against ZnT8A was found in 9.0% for type 1 DM and 10.3% for non-obese adult-onset diabetic patients. In addition, significantly higher signal values in RBA were obtained with the heterodimeric variant. The inclusion of homodimeric immunoreactive peptides revealed the existence of quaternary structure?defined epitopes probably resembling the actual state of the autoantigen in vivo.The main conclusion of this study was that a different pattern of specificity against the ZnT8 autoantigen was exhibited by antibodies elicited in both pathologies: type 1 DM and slowly progressing DM appearing in adults partially masked with adult type 2 DM.