AUTOIMMUNE DISEASE DATABASE AND REPOSITORY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 具有特定特异性的抗核抗体与系统性红斑狼疮有关。初步研究表明，IL-4和促炎细胞因子IL-6、IL-12和IFNy与不同的自身抗体亚群的形成有关。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患者的自身抗体表型也会发生变化。我们假设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的表型，定义为比Chance-Aim 1预测的更频繁地一起产生的一组自身抗体。抗Sm和抗Ku彼此之间有很强的相关性。这些表型的频率将在非裔美国人、高加索人和其他SLE队列中确定。我们将确定自身抗体表型是否与某些细胞因子过度产生的模式相关-目标2。通过使用替代标记物，将直接在血液中测量各种细胞因子，并在受影响的组织中间接测量各种细胞因子。我们将进行前瞻性研究，以探索在小鼠体内产生抗nRNP/Sm自身抗体的IFNy过度生产是否可能增加在人类狼疮中产生自身抗体亚集的风险-AIM 3。我们假设可能有某些狼疮患者过度生产IFNy。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一些显著的血清学差异。与小鼠狼疮一样，人类系统性红斑狼疮可能是几种临床表现重叠但发病机制不同的疾病。

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.