title: Positive autoantibodies to ZnT8 indicate elevated risk for additional autoimmune conditions in patients with Addison's disease.
abstract: Autoimmune Addison's disease (AAD) associates with exceptional susceptibility to develop other autoimmune conditions, including type 1 diabetes (T1D), marked by positive serum autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated protein 2 (IA-2A). Zinc transporter 8 (ZnT8) is a new T1D autoantigen, encoded by the SLC30A8 gene. Its polymorphic variant rs13266634C/T seems associated with the occurrence of serum ZnT8 antibodies (ZnT8A). This study was designed to determine the prevalence of serum ZnT8A and their clinical implication in 140 AAD patients. Other beta cell and thyroid-specific autoantibodies were also investigated, and ZnT8A results were confronted with the rs13266634 genotype. ZnT8A were detectable in 8.5 %, GADA in 20.7 %, IA-2A in 5.7 %, IAA in 1.6 % and various anti-thyroid antibodies in 7.1-67.8 % individuals. Type 1 diabetes was found in 10 % AAD patients. ZnT8A were positive in 57.1 % of T1D patients and 3.4 % non-diabetic AAD. Analysis of ZnT8A enabled to identify autoimmunity in two (14.3 %) T1D individuals previously classified as autoantibody-negative. ZnT8A-positive patients revealed significantly higher number of autoimmune conditions (p < 0.001), increased prevalence of T1D (p < 0.001) and other beta cell-specific autoantibodies. Carriers of the rs13266634 T-allele displayed increased frequency (p = 0.006) and higher titres of ZnT8A (p = 0.002). Our study demonstrates high incidence of ZnT8A in AAD patients. ZnT8A are associated with coexisting T1D and predictive of T1D in non-diabetic subjects. Moreover, positive ZnT8A in AAD indicate elevated risk for additional autoimmune conditions. Autoantibodies to beta cell antigens, comprising ZnT8, could be included in routine screening panels in AAD.
authors.affiliation: Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 49 Przybyszewskiego, 60-355, Poznan, Poland. mfichna@man.poznan.pl.|Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. mfichna@man.poznan.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Fichna
authors.affiliation: Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Anita
authors.initials: A
authors.lastname: Rogowicz-Frontczak
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Żurawek
authors.affiliation: Department of Paediatric Diabetes and Obesity, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Fichna
authors.affiliation: Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 49 Przybyszewskiego, 60-355, Poznan, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Gryczyńska
authors.affiliation: Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Zozulińska-Ziółkiewicz
authors.affiliation: Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 49 Przybyszewskiego, 60-355, Poznan, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Ruchała
mesh_terms: D000224:Addison Disease / Q000097:blood / Q000150:complications / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D027682:Cation Transport Proteins / Q000276:immunology*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000276:immunology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D027682:Cation Transport Proteins; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8
keywords: Addison’s disease; Autoimmunity; Diabetes; ZnT8 autoantibody