Autoimmune Addisons disease (AAD) results from the immune mediated selective destruction of adrenal steroid hormone-secreting cells. Autoantibodies (Abs) against 21-hydroxylase (21OH) are diagnostic present in 8590% newly diagnosed patients. Its genetic susceptibility is conferred by human leukocyte antigen (HLA) DQ2 and DQ8. In many patients autoimmunity extends forming the autoimmune polyglandular syndrome type 2 (APS-2). The aim of this study was to test, whether specific HLA alleles in combination with the 21OHAb status were associated with thyroid autoimmunity as detected by thyroid peroxidase autoantibodies (TPO-Abs) in patients with AAD.
Patients with AAD (n=194) were genotyped for HLA. and TPO-Abs were measured using an enzyme-linked immunosorbent assay, 21OH-Abs with an in vitro transcription/translation method. The titers of Abs were quantified and defined as positive (pos) or negative (neg) (21OH-Ab >48<index; TPOAb >100<UI/ml). Statistical analysis used Kruskall-Wallis and Spearmans correlation tests.
HLA high risk (R) alleles (DQ2 and/or DQ8), 21OHAbpos and TPOAbpos were present in 71, 86 and 36% of the AAD patients, respectively. Furthermore, in order to evaluate the effect of HLA/21OH-Abs status on the production of TPO-Abs the patients were divided into four subgroups (Gr): Gr1: HLAhigh-R/21OH-Abneg; Gr 2: HLAhigh-R/21OH-Abpos; Gr 3:HLAlow-R/21OH-Abneg; Gr4:HLAlow-R/21OH-Abpos. While the Gr 2 and Gr 4 had significantly higher concentration of TPO-Abs in median (44.5 and 55 UI/ml) than Gr 3 (1.3 UI/ml; Pcorrected =7.4 × 10−4 and 7.4 × 10−3 respectively) no difference was observed compared to Gr 1. Also a significant correlation was found between 21OH-Abs and TPO-Abs titers (ρ=0.21, P=0.01).
Both the genetic background of AAD as detected by the HLA risk alleles DQ2/DQ8 and the status of the 21OH-Abs are associated with thyroid autoimmunity in APS-2. This combination may be an indicator of the enhanced risk of polyglandular destruction in autoimmune Addisons disease.
27 Apr - 01 May 2013
European Society of Endocrinology