ALTERED DENDRITIC CELL FUNCTION IN SARCOIDOSIS ANERGY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项探索性研究，旨在评估结节病的无能是否可以通过树突状细胞(DC)数量的减少或DC功能的改变来解释。假设DC功能改变会影响TH2型反应，并与无能有关。研究人员将检查25名结节病患者、17名正常人和数量不详的硬皮病患者：1)髓系和浆细胞样树突状细胞(FACS)的数量和比例；2)分离的DC对异基因混合白细胞增殖试验(MLR)的影响；3)从不同组获得的T细胞的分析；4)无能与上述1-3的相关性；5)上述与疾病活动的相关性。调查人员将招募可能患有结节病的患者，以获得基线实验室信息。然后，患者将回来抽血50毫升，分离树突状细胞，冷冻残留的T细胞，并放置无反应皮肤测试板，在48小时内进行评估。将有一份调查问卷和一系列的分期信息，并在4-6个月内进行再次出血以获得DC的回访。研究人员希望能够在体外设计树突状细胞，在以后的日子里获得更好的功能。他们还将测试T细胞功能在这一工程之后是否会得到改善。T细胞功能改善的评估将基于混合淋巴细胞反应(MLR)和PMA刺激后细胞内细胞因子产生的流式细胞仪评估。由于这是一项探索性研究，统计方法是基于检测到MLR刺激指数(SI)20%的变化。该项目有一位专家合作者(Bhardwaj博士)和一位结节病方面的合格临床专家，可以接触到相当多的患者。

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. This is an exploratory study to assess whether the anergy of sarcoidosis can be explained by either decreased numbers of dendritic cells (DC) or altered function of the DC. The hypothesis is that altered DC function affects the TH2-type response and is associated with anergy. The investigators will examine 25 sarcoid patients, 17 normals and an unspecified number of patients with scleroderma for the following: 1) numbers and ratio of myeloid versus plasmacytoid DC (FACS); 2) effects of isolated DC on allogeneic mixed leukocyte proliferation assay (MLR); 3) analysis of T cells obtained from different groups; 4) correlation of anergy with 1-3 above; 5) correlation of above with disease activity. The investigators will recruit potential patients with Sarcoid to obtain baseline laboratory information. The patients will then return for a 50 ml blood draw to isolate dendritic cells and to freeze residual T cells and to place an anergy skin test panel for evaluation at 48 hours. There will be a questionnaire and a series of staging information obtained from these and a return visit in 4-6 months for a rebleed to obtain DC. The investigators hope to be able to engineer the DC in vitro to get better function at this later date. They will also test whether T-cell function will improve after this engineering. The assessment of better T-cell function will be based on a mixed lymphocyte reaction (MLR) and by flow cytometric evaluation of intracellular cytokine production after PMA stimulation. As this is an exploratory study, the statistical approach is based on the detection of a 20% change in the MLR stimulation index (SI). The project has an expert collaborator (Dr. Bhardwaj) and a qualified clinical expert in sarcoidosis with access to a significant number of patients.