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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的具体目的是：（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，发现表达21-羟化酶自身抗体;（2）将组织相容性复合物人类白细胞抗原（HLA）等位基因和其他免疫遗传决定因素与Addison病进展相关。 阿狄森氏病是一种罕见的自身免疫性疾病（<1/20，000），其易于用糖皮质激素替代治疗，但这种疾病非常罕见，以至于患者仅在危及生命或结束生命的肾上腺危象后才被诊断出来。 认识到Addison病与1型糖尿病的相关性以及抗肾上腺抗体的新自身抗体检测的可用性，我们筛选了约1，000例1型糖尿病患者的21-羟化酶自身抗体表达。 到目前为止，研究人员已经发现了超过15个人与21-羟化酶自身抗体没有一个已知的诊断阿狄森氏病。 其中三个人现在已经被诊断为明显的阿狄森氏病，而其余的人没有肾上腺功能的重大异常，但尚未进行研究，可能检测亚临床异常（血浆肾素活性）。 与此同时，我们发现了阿狄森病与一个特定的HLA等位基因DRB 1 *0404的强相关性，特别是提示性数据，即21-羟化酶自身抗体患者向阿狄森病的进展取决于该DRB 1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DRB 1 *0404患者和不表达DRB 1 *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.