Differences in the humoral autoreactivity to zinc transporter 8 between childhood- and adult-onset type 1 diabetes in Japanese patients.
The aim of this study was to evaluate the humoral autoreactivity to zinc transporter 8 (ZnT8) depending on the clinical phenotype of type 1 diabetes (T1D). ZnT8 autoantibodies (ZnT8A) were determined by radioimmunoassay using carboxy-terminal ZnT8 constructs in 57 childhood-onset, 97 adult-onset, and 85 fulminant T1D. The ZnT8A frequency was higher in childhood-onset patients and decreased with increasing age of onset from 70% to 24% (P(trend)<0.005). None of the patients with fulminant T1D was positive for ZnT8A. There were at least two distinct ZnT8A epitope patterns associated with the aa325-restriction, childhood-onset patients have aa325-nonrestricted response more frequently compared to the adult-onset group (P<0.05). The level of ZnT8A was inversely associated with the copy number of HLA-DR4 allele (P<0.05). These results suggest differences in the humoral autoreactivity to ZnT8 depending on the clinical phenotype, which should provide strategy for autoantibody measurement in subjects to allow early diagnosis of autoimmune T1D.
Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital, Nagasaki, Japan. eijikawa@nagasaki-u.ac.jp
Eiji
E
Kawasaki
Kan
K
Nakamura
Genpei
G
Kuriya
Tsuyoshi
T
Satoh
Masakazu
M
Kobayashi
Hironaga
H
Kuwahara
Norio
N
Abiru
Hironori
H
Yamasaki
Nobuo
N
Matsuura
Junnosuke
J
Miura
Yasuko
Y
Uchigata
Katsumi
K
Eguchi
D000293:Adolescent; D000328:Adult; D044466:Asian People; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015551:Autoimmunity; D027682:Cation Transport Proteins / Q000235:genetics / Q000276:immunology*; D002648:Child; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D015804:HLA-DR4 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral; D050417:Insulin-Secreting Cells / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000075703:Zinc Transporter 8
D001323:Autoantibodies; D027682:Cation Transport Proteins; D000939:Epitopes; D015804:HLA-DR4 Antigen; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8