Since individuals with Addison’s disease (AD) present considerable co-occurrence of additional autoimmune conditions, clustering of autoimmunity was also predicted among their relatives. The study was aimed to evaluate circulating autoantibodies in first-degree relatives of patients with AD and to correlate them with the established genetic risk factors (PTPN22 rs2476601, CTLA4 rs231775, and BACH2 rs3757247). Antibodies were evaluated using validated commercial assays and genotyping was performed with TaqMan chemistry. The studied cohort comprised 112 female and 75 male relatives. Circulating autoantibodies were found in 69 relatives (36.9%). Thyroid autoantibodies, aTPO and aTg were detectable in 25.1% and 17.1% relatives, respectively. Antibodies to 21-hydroxylase (a21OH) were found 5.8% individuals, and beta cell-specific antibodies to ZnT8, GAD and IA2 – in 7.5%, 8.0% and 2.7%, respectively. The prevalence of a21OH (p=0.0075; OR 7.68; 95% CI 1.903-36.0), aTPO (p<0.0001; OR 3.85; 95%CI 1.873-7.495) and aTg (p<0.0001; OR 7.73; 95% CI 3.112-19.65), as well as aGAD (p=0.0303; OR 3.38; 95% CI 1.180-9.123) and aZnT8 (p=0.032; OR 6.40; 95% CI 1.846-21.91) was significantly increased in carriers of rs2476601 T allele. Moreover, T allele appeared to be risk factor for multiple circulating autoantibody specificities (p=0.0009; OR 5.79; 95% CI 1.962-15.81). None of the studied autoantibodies demonstrated significant association with rs231775 in CTLA4 (p<0.05), and only weak association was detected between BACH2 rs3757247 and circulating aTPO (p=0.0336; OR 2.12; 95%CI 1.019-4.228). In conclusion, first-degree relatives of patients with AD, carriers of the PTPN22 rs2476601 T allele, are at particular risk of developing autoantibodies to the endocrine antigens.
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