IMMUNOGENETICS--TARGET ORGAN DAMAGE IN IMMUNE NEPHRITIS

免疫遗传学——免疫性肾炎的靶器官损伤

• 批准号: 6895575
• 负责人: CHANDRA MOHAN
• 金额: $ 41.49万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895575
• 关键词: autoantibody; autoimmune disorder; cellular pathology; flow cytometry; gene expression; genetic mapping; genetic susceptibility; genotype; immunogenetics; immunopathology; laboratory mouse; nephritis; statistics /biometry

DESCRIPTION (provided by applicant): Target organ damage can ensue from several different primary triggers. One group of such primary triggers includes pathogenic autoantibodies that have affinity for glomerular antigens. Thus, it is clear that "nephrophilic" or "nephrotoxic" antibodies have the potential to target to the kidneys and compromise renal function. Currently, little is known about the genetic factors or the cellular players that determine the extent of target organ damage in immune nephritis. The long-term objective of this proposal is to shed light on these issues. This proposal aims to achieve this in several different ways. We have recently discovered that the 129/svJ strain demonstrates increased target organ damage when exposed to nephrophilic autoantibodies. In the first aim, we will identify the genetic loci that are responsible for the increased nephritis seen in 129/svJ mice. In the second aim, the impact of nephritis susceptibility loci on systemic immunity as well as renal disease will be studied. Finally, we will ascertain how nephritis susceptibility loci might impact the function of resident glomerulocytes in these mice. Collectively, these studies will deepen our understanding of the genetic factors and cellular elements leading to nephritis, particularly in systemic autoimmune diseases such as lupus. A better understanding of the genetic and cellular basis of target organ damage could potentially lead to more targeted therapies for nephritis in the future.

描述（由申请人提供）： 靶器官损伤可以由几种不同的主要触发因素引起。一组这样的初级触发物包括对肾小球抗原具有亲和力的致病性自身抗体。因此，很明显，“亲肾性”或“肾毒性”抗体具有靶向肾脏并损害肾功能的潜力。目前，对决定免疫性肾炎靶器官损伤程度的遗传因素或细胞因素知之甚少。本提案的长期目标是阐明这些问题。本提案旨在以几种不同的方式实现这一目标。我们最近发现，129/svJ菌株暴露于嗜肾性自身抗体时，靶器官损伤增加。在第一个目标中，我们将确定导致129/svJ小鼠肾炎增加的遗传位点。在第二个目标中，将研究肾炎易感基因座对全身免疫以及肾脏疾病的影响。最后，我们将确定肾炎易感基因位点如何影响这些小鼠中常驻肾小球细胞的功能。总的来说，这些研究将加深我们对导致肾炎的遗传因素和细胞因素的理解，特别是在系统性自身免疫性疾病如狼疮中。更好地了解靶器官损伤的遗传和细胞基础可能会在未来导致更多的肾炎靶向治疗。