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受到限制。在诊断或疾病病程中获得的患者样本中，没有进行结节病的动物模型，并进行了人类研究。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注射的组织的研究表明，CD4淋巴细胞和巨噬细胞的募集逐渐形成成熟的上皮细胞，巨细胞和淋巴细胞的RIM，这些细胞形成了曲棍球肉芽肿。在这段时间内没有研究基因表达的时间序列，因为肉芽瘤出现。 Kveim成熟期间的基因表达微阵列分析提供了一个独特的机会，可以研究一系列分子生物学事件，从而导致肉芽肿形成。 我们建议招募5至8例最近进行KS测试阳性的患者，以诊断其疾病。将进行四次皮下注射。在KS悬架孵育后，将在1天，1周，2周和4周进行活检。对于对照，每个患者将进行正常皮肤活检。基因表达谱将通过微阵列分析确定，并与组织学变化有关。微阵列将通过RT PCR和免疫组织化学验证基因表达。识别响应KS悬浮液表示的基因将提供有关颗粒瘤形成的开始的新信息，为将来的研究提供了更大的方向，并可以帮助确定新的潜在干预目标。