Grant: $54,000 - National Institutes of Health - Sep. 18, 2009
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Award Description: This is an administrative supplement for a parent grant Characterization of dendritic cells in psoriasis and the effects of efalizumab, 1K23AR052404. The goals of the parent grant are to study the dendritic cells (DCs) in the skin and blood in normal volunteers and patients with psoriasis during treatment with this anti-CD11a (integrin) biologic therapy. The aims of this supplement are within this aim, to more fully evaluate an adverse event that occurs on ceasing therapy, namely a severe recurrence of disease on ceasing efalizumab. We had collected and archived samples that would allow us to characterize the cellular infiltrate and genomic profile of this adverse event. Eight patients in our trial experienced this reaction, and we have precious material available to study this. We will perform a panel of antibodies to determine which leukocyte populations are increased, as well as immunofluorescence to determine if TNF- and iNOS-producing DCs (TIP-DCs) are also increased in the recurrent lesions. We will perform a genomic analysis of these skin lesions to more fully characterize the response to efalizumab and the recurrent eruption. In addition, we will use material from this clinical trial to characterize a new population of myeloid DCs, termed slanDCs. These are circulating myeloid DCs capable of priming T cell responses, and produce IL-12 and TNF on stimulation with LPS. This may be a positive marker of inflammatory TIP-DCs. While slanDCs have been identified in psoriasis tissue, the effects of treatment have not yet been studied. The antibody to study this population has recently become commercially a available, allowing immunohistochemistry and immunofluorescence to be performed. The opportunity to study a new population of myeloid DCs in psoriasis is unique, and will be applicable to other inflammatory diseases.
Project Description: As identified in Award Description.
Jobs Summary: 00 (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 18, 2009. Help expand these official descriptions using the wiki below.