title: Long-term sustained autoimmune response to beta cell specific zinc transporter (ZnT8, W, R, Q) in young adult patients with preserved beta cell function at diagnosis of diabetes.
abstract: The aim of this study was to examine whether autoantibodies to: ZnT8-Tryptophan (ZnT8WA), ZnT8-Arginine (ZnT8RA) or ZnT8-Glutamine (ZnT8QA) correlated with C-peptide or other autoantibodies and to assess diagnostic sensitivity of ZnT8WRQA. Specimens from 270 newly diagnosed diabetic subjects (age 15-34 years) and after 5 years duration of disease were examined. Four linear regression models were used to dissect the importance of different factors from diagnosis for the respective difference of (logZnT8WA), (logZnT8RA) and (logZnT8QA); A) unadjusted model for: initial C-peptide, age, BMI, gender, clinical classification, ICA, GADA, IA-2A, (ZnT8WA/ZnT8RA/ZnT8QA); B) C-peptide corrected for clinical factors; C) C-peptide corrected for autoantibodies; D) C-peptide corrected for all factors. The least decrease of ZnT8WA was observed in patients with high initial C-peptide in all models A) p = 0.054; B) p = 0.021; C) p = 0.047 and D) p = 0.017. A less statistically significant decrease of ZnT8RA was observed in patients with high initial C-peptide in A) p = 0.038 and C) p = 0.047, but this finding was not confirmed in B or D. The decrease of ZnT8QA levels was not related to C-peptide in any model but correlated to age D) p = 0.049. Furthermore, patients with unclassifiable diabetes showed the least decrease in D) p = 0.035. ZnT8WA, ZnT8RA or ZnT8QA were identified as a single autoantibody in 3.8% (10/266) of patients, thereby increasing diagnostic sensitivity from 79.3% (211/266) to 83.1% (221/266). In conclusion, high initial C-peptide was the most important factor even after adjusting for other factors in patients positive for ZnT8WA or ZnT8RA to remain autoantibody positive 5 years after diagnosis.
authors.affiliation: Department of Clinical Sciences, Lund University, Skåne University Hospital, SUS, Malmö, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Ingemansson
authors.forename: Fariba
authors.initials: F
authors.lastname: Vaziri-Sani
authors.forename: Ulf
authors.initials: U
authors.lastname: Lindblad
authors.forename: Soffia
authors.initials: S
authors.lastname: Gudbjornsdottir
authors.forename: Carina
authors.initials: C
authors.lastname: Törn
mesh_terms: D000293:Adolescent; D000328:Adult; D002096:C-Peptide / Q000097:blood / Q000276:immunology*; D027682:Cation Transport Proteins / Q000097:blood / Q000276:immunology*; D003920:Diabetes Mellitus / Q000276:immunology*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology*; D016014:Linear Models; D008297:Male; D011446:Prospective Studies; D012372:ROC Curve; D011863:Radioimmunoassay; D013548:Sweden; D055815:Young Adult; D000075703:Zinc Transporter 8
chemical_list: D002096:C-Peptide; D027682:Cation Transport Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8