PREDICTION & DIAGNOSIS OF ADDISON'S DIS/IMMUNOGENETICS OF POLYGLANDULAR FAILURE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。该研究的具体目的是：(1)前瞻性评估表达21-羟化酶自身抗体的1型糖尿病或其他自身免疫性疾病及其亲属患者的肾上腺功能；(2)组织相容性复合物人白细胞抗原（HLA）等位基因和其他免疫遗传决定因素与Addison病进展的相关性。阿狄森氏病是一种罕见的自身免疫性疾病（<1/20,000），很容易用糖皮质激素替代治疗，但这种疾病非常罕见，以至于患者经常在危及生命或危及生命的肾上腺危机后才被诊断出来。认识到Addison's病与1型糖尿病的关联以及抗肾上腺抗体的新自身抗体检测的可用性，我们筛选了大约1000名1型糖尿病患者21-羟化酶自身抗体的表达。到目前为止，研究人员已经发现超过15个患有21-羟化酶自身抗体的人没有被诊断为Addison病。其中3人已被诊断为明显的Addison病，其余的人没有明显的肾上腺功能异常，但尚未进行可能检测亚临床异常（血浆肾素活性）的试验研究。同时，我们发现Addison's病与一个特定的HLA等位基因DRB1*0404有很强的相关性，特别是在具有21-羟化酶自身抗体的患者中，Addison's病的进展依赖于这个DRB1组织相容性标记。本提案旨在更好地定义表达21-羟化酶自身抗体的DRB1*0404患者和非DRB1*0404患者的肾上腺功能，重要的是将提供前瞻性信息。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The specific aims of the study are to: (1) prospectively evaluate adrenal function in patients with type 1 diabetes, or other autoimmune disorders and their relatives, found to express 21-hydroxylase autoantibodies and (2) correlate histocompatibility complex human leukocyte antigen (HLA) alleles and additional immunogenetic determinants with progression to Addison's disease. Addison's disease is a rare autoimmune disorder (<1/20,000), which is readily treated with glucocorticoid replacement, but a disorder which is so rare that not infrequently patients are diagnosed only after life threatening, or life ending adrenal crisis. Recognizing the association of Addison's disease with type 1 diabetes and the availability of a new autoantibody assay for anti-adrenal antibodies, we have screened approximately 1,000 patients with type 1 diabetes for the expression of 21-hydroxylase autoantibodies. To date, investigators have found more than 15 individuals with 21-hydroxylase autoantibodies without a known diagnosis of Addison's disease. Three of these individuals have now been diagnosed with overt Addison's disease, while the remainder do not have a major abnormality of adrenal function, but have not been studied with tests likely to detect subclinical abnormalities (plasma renin activity). At the same, time we have discovered a strong association of Addison's disease with a specific HLA allele, DRB1*0404, and in particular suggestive data, that progression to Addison's disease amongst patients with 21-hydroxylase autoantibodies is dependent upon this DRB1 histocompatibility marker. The present proposal is designed to better define adrenal function of patients with and without DRB1*0404, who express 21-hydroxylase autoantibodies, and importantly will provide prospective information.