AUTOIMMUNE DISEASE DATABASE AND REPOSITORY

自身免疫性疾病数据库和存储库

• 批准号: 7717070
• 负责人: WESTLEY H REEVES
• 金额: $ 34.41万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7717070
• 关键词: Affect; African American; Antinuclear Antibodies; Autoantibodies; Autoimmune Diseases; Autoimmunity; Blood; Caucasians; Caucasoid Race; Clinical; Computer Retrieval of Information on Scientific Projects Database; Databases; Disease; Early Diagnosis; Employee Strikes; Frequencies; Funding; Grant; Human; Institution; Interferons; Lupus; Measures; Mediating; Modeling; 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. We hypothesize that, as in the mouse, cytokine overproduction may be a critical factor determining autoantibody specificity, i.e. autoantibody phenotypes in SLE may be markers for different forms of SLE mediated by different cytokines. Several predictions of this model will be evaluated. We will look for human autoantibody phenotypes, defined as groups of autoantibodies produced together more frequently than predicted by chance. For instance, anti-Sm and anti-Ku are strongly associated with one another. We expect to find additional examples. The frequencies of these phenotypes will be determined in African-American, Caucasian, and other SLE cohorts. We will then determine whether the autoantibody phenotypes correlate with certain patterns of cytokine overproduction. A variety of cytokines, some of them contributing to autoantibody formation in mice, will be measured directly in the blood and indirectly in affected tissues with surrogate markers. Finally, we will carry out prospective studies to explore the possibility that the overproduction of IFN, which drives anti-nRNP/Sm autoantibody production in mice, increases the risk of developing a subset of autoantibodies in human lupus. We hypothesize that there may be certain lupus patients, including many African-Americans, who overproduce IFN. 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. Thus, like murine lupus, human SLE may be several diseases with overlapping clinical manifestations but a different pathogenesis. If so, there could be significant implications for the early diagnosis of autoimmunity and its treatment.

这个子项目是许多研究子项目中的一个 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。 我们假设，在小鼠中，细胞因子的过度产生可能是决定自身抗体特异性的关键因素，即SLE中的自身抗体表型可能是由不同细胞因子介导的不同形式的SLE的标志物。 将评估该模型的几个预测。 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。 例如，抗Sm和抗Ku彼此强烈相关。 我们希望找到更多的例子。 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。 然后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。 多种细胞因子，其中一些有助于小鼠自身抗体形成，将直接在血液中测量，并间接在受影响的组织中与替代标记物。 最后，我们将进行前瞻性研究，以探讨IFN的过度生产，这驱动抗nRNP/Sm自身抗体在小鼠中的生产，增加人类狼疮中发展自身抗体的一个子集的风险。 我们推测，可能有某些狼疮患者，包括许多非洲裔美国人，谁过度产生干扰素。 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。因此，像鼠狼疮，人类SLE可能是几种疾病重叠的临床表现，但不同的发病机制。 如果是这样的话，可能对自身免疫的早期诊断和治疗有重要意义。