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.
Highlights
Individuals suffering from the autoimmune Addison’s disease (AAD) display remarkable susceptibility to develop other autoimmune conditions, in particular organ-specific comorbidities, such as autoimmune thyroid disease (AITD), type 1 diabetes (T1D) and pernicious anaemia
ZnT8 antibodies (ZnT8A) were detectable in 8.5 %, glutamic acid decarboxylase (GADA) in 20.7 %, IA-2A in 5.7 %, IAA in 1.6 % and various anti-thyroid antibodies in 7.1–67.8 % individuals
21 (15 %) patients presented with isolated AAD, two siblings suffered from autoimmune polyendocrine syndromes (APS) type 1, whereas all other participants displayed either APS type 2 or 4, with up to five coexisting autoimmune conditions [3]
Summary
Individuals suffering from the autoimmune Addison’s disease (AAD) display remarkable susceptibility to develop other autoimmune conditions, in particular organ-specific comorbidities, such as autoimmune thyroid disease (AITD), type 1 diabetes (T1D) and pernicious anaemia. Typical disease combinations are classified into distinct autoimmune polyendocrine syndromes (APS) and present significant challenge in clinical management of the AAD patients [3, 4]. The combination of AAD with T1D seems disadvantageous. These patients may present with recurrent hypoglycaemic episodes, due to decreased gluconeogenesis and enhanced insulin sensitivity during glucocorticoid shortage [5]. AAD individuals require close follow-up with regard to their diabetic risk. Both disorders share several similarities including predisposing genetic alleles and T cellmediated destruction of the endocrine tissue. AAD as well as T1D manifest with organ-specific autoantibodies, which are markers of an on-going autoimmune process detectable prior to clinical presentation. Recently discovered zinc transporter 8 autoantibodies (ZnT8A) have not been investigated in patients with AAD to date
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