AUTOIMMUNE DISEASE DATABASE AND REPOSITORY

自身免疫性疾病数据库和存储库

• 批准号: 7950700
• 负责人: WESTLEY H REEVES
• 金额: $ 13.18万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950700
• 关键词: Affect; African American; Antinuclear Antibodies; Autoantibodies; Autoimmune Diseases; Blood; Caucasians; Caucasoid Race; Clinical; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Databases; Disease; Employee Strikes; Frequencies; Funding; Grant; Human; Institution; Interleukin-12; Interleukin-4; Interleukin-6; Lupus; Measures; Mus; Pathogenesis; Patients; Pattern; Phenotype; Production; Prospective Studies; Race; Research; Research Personnel; Resources; Risk; Serological; Source; Specificity; Surrogate Markers; Systemic Lupus Erythematosus; Tissues; United States National Institutes of Health; cohort; cytokine; repository

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. Antinuclear antibodies of particular specificities are associated with systemic lupus erythematosus-SLE. Preliminary studies implicate IL-4 and the proinflammatory cytokines IL-6, IL-12, and IFNy in the formation of different subsets of autoantibodies. Cytokine overproduction may be a key factor determining the autoantibody phenotype. We have found that autoantibody phenotypes in SLE patients also can change. We hypothesize that cytokine overproduction may be a critical factor determining autoantibody specificity. We will look for human autoantibody phenotypes, defined as groups of autoantibodies produced together more frequently than predicted by chance- Aim 1. Anti-Sm and anti-Ku are strongly associated with one another. The frequencies of these phenotypes will be determined in African-American, Caucasian, and other SLE cohorts. We will determine whether the autoantibody phenotypes correlate with certain patterns of cytokine overproduction-Aim 2. A variety of cytokines will be measured directly in the blood and indirectly in affected tissues through the use of surrogate markers. We will carry out prospective studies to explore the possibility that the overproduction of IFNy, which drives anti-nRNP/Sm autoantibody production in mice, increases the risk of developing a subset of autoantibodies in human lupus-Aim 3. We hypothesize that there may be certain lupus patients who overproduce IFNy. Another group of SLE patients, most commonly Caucasians, may overproduce a different set of cytokines. This may help explain some of the striking serological differences between races. Like murine lupus, human SLE may be several diseases with overlapping clinical manifestations but a different pathogenesis.

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， 因此可以在其他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。 特异性抗核抗体与系统性红斑狼疮相关。 初步研究表明IL-4和促炎细胞因子IL-6、IL-12和IFN γ参与不同的自身抗体亚群的形成。 细胞因子的过度产生可能是决定自身抗体表型的关键因素。 我们发现SLE患者自身抗体表型也会发生改变。 我们推测细胞因子的过度产生可能是决定自身抗体特异性的一个关键因素。 我们将寻找人类自身抗体表型，定义为比偶然预测更频繁地一起产生的自身抗体组-目的1。 抗Sm抗体和抗Ku抗体相互之间有很强的相关性。 将在非裔美国人、高加索人和其他SLE队列中确定这些表型的频率。 我们将确定自身抗体表型是否与某些细胞因子过度产生模式相关-目的2。 将直接在血液中测量各种细胞因子，并通过使用替代标志物间接测量受影响组织中的细胞因子。 我们将进行前瞻性研究，以探索IFN γ的过度产生（其驱动小鼠中抗nRNP/Sm自身抗体的产生）增加在人狼疮-Aim 3中产生自身抗体子集的风险的可能性。 我们假设可能有某些狼疮患者过度产生IFN γ。 另一组SLE患者，最常见的是高加索人，可能会过度产生一组不同的细胞因子。 这可能有助于解释种族之间的血清学差异。 与鼠狼疮一样，人类SLE可能是几种临床表现重叠但发病机制不同的疾病。