ALTERED DENDRITIC CELL FUNCTION IN SARCOIDOSIS ANERGY

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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.