Division of Rheumatology Division of EndocrinologyDiabetes, and Metabolism, College of Medicine, Milton S Hershey Medical Center, The Pennsylvania State University, Mail Code H044, 500 University Drive, Hershey, Pennsylvania 17033-0850, USA.
Endocr Connect. 2014 May 6;3(2):99-109. doi: 10.1530/EC-14-0039. Print 2014.
Clinical and experimental evidence support a role for gonadal steroids in modulating the expression and course of autoimmune diseases such as lupus. Whether or not inherited variation in sensitivity to circulating androgenic hormones could influence the manifestations of such disease is, however, unknown. We sought to determine whether differences in androgen sensitivity conferred by variation in the exon 1 CAG repeat region of the androgen receptor (AR) gene were associated with differences in the clinical or humoral immune manifestations of lupus in a cohort of female subjects. We found that shorter AR CAG repeat lengths in lupus subjects correlated with a higher Systemic Lupus Erythematosus Disease Activity Index score, higher ANA levels, and expression of a broader array of IgG autoantibodies. Our findings of more severe clinical manifestations and more exuberant humoral autoimmunity in women with a shorter AR exon 1 CAG repeat length suggest a role for genetically determined sensitivity to androgens as a modulator of autoimmune processes.
临床和实验证据支持性腺类固醇在调节自身免疫性疾病（如狼疮）的表达和病程中的作用。然而，遗传敏感性的变化是否会影响这种疾病的表现尚不清楚。我们试图确定雄激素受体（AR）基因外显子 1 CAG 重复区域的变异所赋予的雄激素敏感性差异是否与狼疮患者的临床或体液免疫表现的差异相关。我们发现，狼疮患者的 AR CAG 重复长度较短与系统性红斑狼疮疾病活动指数评分较高、抗核抗体水平较高以及更广泛的 IgG 自身抗体表达相关。我们发现，AR 外显子 1 CAG 重复长度较短的女性患者具有更严重的临床症状和更旺盛的体液自身免疫，这表明遗传决定的对雄激素的敏感性可能是自身免疫过程的调节剂。
