Gene Expression Profiling of the Kveim Siltzbach Test

Kveim Siltzbach 测试的基因表达谱

• 批准号: 6816495
• 负责人: MICHAEL C IANNUZZI
• 金额: $ 21.19万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-09 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6816495
• 关键词: biopsy; clinical research; gene expression profiling; granuloma; human subject; immunocytochemistry; immunologic skin test; immunopathology diagnosis; laser capture microdissection; microarray technology; polymerase chain reaction; sarcoidosis; suspensions

DESCRIPTION (provided by applicant): Approaches to define early gene expression in sarcoidal granuloma formation have been limited. No animal model for sarcoidosis exists and human studies have been carried out in patient samples obtained at diagnosis or during the disease course. Previous studies performed at Mt. Sinai and elsewhere have shown that the cellular and biochemical granulomatous response to Kveim-Siltzbach (KS) suspension parallels the disease granuloma. Studies of KS injected tissue harvested at weeks 1, 2, 3 and 4 have revealed recruitment of CD4 lymphocytes and macrophages that gradually form the mature epithelioid cells, giant cells, and rim of lymphocytes that form the sarcoidal granuloma. There are no studies of the temporal sequence of gene expression during this time period as granulomas emerge. Gene expression microarray analyses during Kveim maturation offer a unique opportunity to investigate the cascade of molecular biologic events leading to granuloma formation. We propose to recruit 5 to 8 patients who recently had positive KS tests for the diagnosis of their illness. Four subcutaneous injections will be performed. Sites will be biopsied a 1 day, 1 week, 2 weeks, and 4 weeks after incubation of KS suspension. For controls each patient will have a biopsy of normal skin. Gene expression profiles will be determined by microarray analysis and related to histological changes. Gene expression results by microarray will be verified by RT PCR and immunohistochemisty. Identifying genes expressed in response to the KS suspension will provide new information about the initiation of granuloma formation, give greater direction to future studies and could help identify new potential targets for intervention.

描述（由申请人提供）： 定义结节肉芽肿形成中早期基因表达的方法有限。不存在结节病的动物模型，并且已经对诊断时或病程期间获得的患者样本进行了人体研究。先前在西奈山和其他地方进行的研究表明，对 Kveim-Siltzbach (KS) 悬浮液的细胞和生化肉芽肿反应与疾病肉芽肿相似。对第 1、2、3 和 4 周收获的 KS 注射组织的研究表明，CD4 淋巴细胞和巨噬细胞的募集逐渐形成成熟的上皮样细胞、巨细胞和淋巴细胞边缘，从而形成肉芽肿。目前还没有关于肉芽肿出现期间基因表达时间顺序的研究。 Kveim 成熟过程中的基因表达微阵列分析为研究导致肉芽肿形成的分子生物学事件级联提供了独特的机会。 我们建议招募 5 至 8 名最近 KS 测试呈阳性的患者来诊断他们的疾病。将进行四次皮下注射。 KS悬浮液孵育后1天、1周、2周和4周对位点进行活检。对于对照，每个患者都将进行正常皮肤的活检。基因表达谱将通过微阵列分析确定并与组织学变化相关。微阵列的基因表达结果将通过RT PCR和免疫组织化学进行验证。鉴定对 KS 悬浮液反应而表达的基因将提供有关肉芽肿形成起始的新信息，为未来的研究提供更大的方向，并有助于确定新的潜在干预目标。