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

预言

• 批准号: 7604367
• 负责人: GEORGE S EISENBARTH
• 金额: $ 0.17万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604367
• 关键词: Addison' s disease; Adrenal Glands; Alleles; Anti-Adrenal; Antibodies; Autoantibodies; Autoimmune Diseases; Biological Assay; Computer Retrieval of Information on Scientific Projects Database; Data; Diagnosis; Disease; Failure; Funding; Glucocorticoids; Grant; HLA Antigens; Histocompatibility; Immunogenetics; Individual; Institution; Insulin-Dependent Diabetes Mellitus; Life; Major Histocompatibility Complex; Patients; Plasma; Relative (related person); Renin; Research; Research Personnel; Resources; Source; Steroid 21-Monooxygenase; Testing; Time; United States National Institutes of Health; design; end of life; prospective

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它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患者及其亲属的肾上腺功能；(2) 将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艾迪生病进展相关联。 艾迪生氏病是一种罕见的自身免疫性疾病（<1/20,000），很容易通过糖皮质激素替代治疗来治疗，但这种疾病非常罕见，以至于不少患者只有在危及生命或结束生命的肾上腺危象后才被诊断出来。 认识到阿狄森氏病与 1 型糖尿病的关联以及抗肾上腺抗体的新型自身抗体测定的可用性，我们对大约 1,000 名 1 型糖尿病患者进行了 21-羟化酶自身抗体表达的筛查。 迄今为止，研究人员已发现超过 15 名患有 21-羟化酶自身抗体但未诊断出阿狄森氏病的人。 其中三人现已被诊断患有明显的阿狄森氏病，而其余的人没有肾上腺功能的重大异常，但尚未进行可能检测亚临床异常（血浆肾素活性）的测试。 与此同时，我们发现阿狄森氏病与特定的 HLA 等位基因 DRB1*0404 存在很强的相关性，特别是提示性数据，具有 21-羟化酶自身抗体的患者进展为阿狄森氏病取决于这种 DRB1 组织相容性标记。 本提案旨在更好地定义表达 21-羟化酶自身抗体的有或无 DRB1*0404 患者的肾上腺功能，重要的是将提供前瞻性信息。