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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的具体目的是：(1)前瞻性评估1型糖尿病或其他自身免疫性疾病患者及其亲属的肾上腺功能，发现这些患者表达21-羟基酶自身抗体；(2)组织相容性复合体人类白细胞抗原(HLA)等位基因和其他免疫遗传决定因素与Addison病的进展相关。爱迪生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，但这种疾病是如此罕见，以至于患者只有在危及生命或结束生命的肾上腺危机后才被诊断出来。认识到爱迪生病与1型糖尿病的关联，以及一种新的抗肾上腺抗体的自身抗体检测方法的可用性，我们对大约1000名1型糖尿病患者进行了21-羟基酶自身抗体的表达筛查。到目前为止，研究人员已经发现了超过15名患有21-羟基酶自身抗体的人，但没有已知的爱迪生病的诊断。这些患者中有三人现已被诊断出患有显性爱迪生病，其余的人没有重大的肾上腺功能异常，但还没有进行可能检测到亚临床异常的测试(血浆肾素活性)。同时，我们发现Addison病与一种特定的HLA等位基因DRB1*0404有很强的相关性，尤其是有提示意义的数据，即具有21-羟基酶自身抗体的患者进展为Addison病依赖于该DRB1组织相容性标记物。目前的建议旨在更好地确定表达21-羟基酶自身抗体的DRB1*0404患者和不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.