ALTERED DENDRITIC CELL FUNCTION IN SARCOIDOSIS ANERGY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这是一项探索性研究，旨在评估结节病的无反应性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。 该假说是DC功能改变影响TH 2型反应并与无反应性相关。 研究者将检查25名结节病患者、17名正常人和数目不详的硬皮病患者的以下内容：1）髓样与浆细胞样DC（FACS）的数目和比率; 2）分离的DC对同种异体混合白细胞增殖测定（MLR）的影响; 3）从不同组获得的T细胞的分析; 4）无反应性与上述1-3的相关性;（5）上述指标与病情活动的相关性。 研究者将招募潜在的结节病患者，以获得基线实验室信息。 然后，患者将返回进行50 ml抽血，以分离树突状细胞并冷冻残留的T细胞，并放置无反应性皮肤测试板以在48小时进行评估。 将有一份问卷和一系列分期信息，并在4-6个月内进行回访，以再次出血获得DC。 研究人员希望能够在体外设计DC，以便在稍后的日期获得更好的功能。 他们还将测试T细胞功能是否会在这种工程改造后得到改善。 更好的T细胞功能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术评价。 由于这是一项探索性研究，统计方法基于检测到MLR刺激指数（SI）变化20%。 该项目有一名专家合作者（Bhardwaj博士）和一名合格的结节病临床专家，可接触大量患者。

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.