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

预言

• 批准号: 7377761
• 负责人: GEORGE S EISENBARTH
• 金额: $ 0.09万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377761
• 关键词: PREDICTION; DIAGNOSIS; ADDISON; DIS; IMMUNOGENETICS

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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。该研究的具体目的是：（1）前瞻性评估1型糖尿病患者或其他自身免疫性疾病及其亲属的肾上腺功能，发现表达21-羟化酶自身抗体，（2）将组织抗体性复杂的人白细胞抗原（HLA）与其他免疫源性相关联。艾迪生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，但这种疾病极为罕见，以至于不经常诊断出患者在威胁生命或生命结束生命后被诊断出来。认识到艾迪生氏病与1型糖尿病的关联以及用于抗肾上腺抗体的新自身抗体测定的可用性，我们已经筛选了大约1,000名1型1型糖尿病患者，以表达21-羟化酶自动抗体的表达。迄今为止，研究人员已经发现15个患有21-羟化酶自身抗体的人，没有艾迪生氏病的已知诊断。现在，其中三个人被诊断出患有明显的艾迪生氏病，而其余的人则没有肾上腺功能的主要异常，但尚未对可能检测到亚临床异常的测试进行研究（血浆肾素活性）。在同一时间，我们发现了艾迪生氏病与特定的HLA等位基因，DRB1*0404，尤其是暗示性数据的紧密关联，在21-羟化酶自身抗体的患者中，艾迪生氏病的进展取决于此DRB1组织相容性标记。本提案旨在更好地定义有或没有DRB1*0404患者的肾上腺功能，这些患者表达21-羟化酶自身抗体，重要的是将提供前瞻性信息。