ALTERED DENDRITIC CELL FUNCTION IN SARCOIDOSIS ANERGY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项探索性研究，旨在评估结节病的能量是否可以通过树突状细胞（DC）数量减少或DC功能改变来解释。假设改变的DC功能影响th2型反应，并与能量有关。研究人员将对25例肉瘤患者、17例正常人和数量不明的硬皮病患者进行以下检查：1)髓细胞样DC与浆细胞样DC （FACS）的数量和比例；2) DC对同种异体混合白细胞增殖试验（MLR）的影响；3)各组T细胞分析；4)能量与以上1-3的相关性；5)以上与疾病活动度的相关性。研究者将招募潜在的肉瘤患者来获得基线实验室信息。然后，患者将返回进行50毫升的抽血，以分离树突状细胞并冷冻残留的T细胞，并在48小时内放置能量皮肤测试板进行评估。将会有一份调查问卷和一系列的分期信息从中获得，并在4-6个月内进行复诊以获得DC。研究人员希望能够在体外设计DC，以便在晚些时候获得更好的功能。他们还将测试t细胞的功能是否会在这项工程后得到改善。评估更好的t细胞功能将基于混合淋巴细胞反应（MLR）和流式细胞术评估PMA刺激后细胞内细胞因子的产生。由于这是一项探索性研究，因此统计方法是基于检测到MLR增产指数（SI）的20%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，可以接触到大量患者。

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.