Dendritic Cells in Patients With Acute or Chronic Skin Graft Versus Host Disease

Study Overview
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Brief Summary
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Dendritic cells (DCs) serve as sentries for the immune system. DCs recognize foreign compounds (antigens) in the body, which they internalize and process. When DCs uptake foreign antigens, they migrate to secondary lymphoid organs, where the processed antigens are presented to T cells. Various DC subsets with unique cell lineages, surface protein markers, and tissue localization determinants have been identified. For example, Langerhans cells (LCs) and interstitial dendritic cells (intDCs) are DCs found in stratified epithelia, such as the skin. Though both are expressed in the skin, they differ with respect to their origin and surface protein content and can activate distinct types of immune responses. They may also have different specificities for the capture of antigens and presentation to circulating T cells. To date, it is unknown what role, if any, the different DC populations that reside or repopulate in the skin play in the development and progression of skin graft-versus-host disease (GVHD) following bone marrow transplant.

Official Title
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Analysis of Dendritic Cells in Patients With Acute or Chronic Skin Graft Versus Host Disease

Conditions
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Acute Graft-versus-host Disease, Acute GVHD, Chronic Graft-versus-host Disease, Chronic GVHD

Intervention / Treatment
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* Procedure: Skin punch biopsy
* Procedure: Peripheral blood draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 years of age at enrollment Willing and able to sign the informed consent Current diagnosis/suspected diagnosis of acute skin GVHD OR Current diagnosis/suspected diagnosis of chronic skin GVHD Exclusion Criteria: Known infection with Hepatitis B or C, HTLV, or HIV Pregnant females

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Arm 1: Acute skin GVHD<br>When clinically indicated, patients will undergo a skin biopsy to confirm a suspected diagnosis of acute or chronic GVHD, or to assess the status of their previously diagnosed acute or chronic GVHD. After the necessary samples are obtained for optimal medical care of the patient, two 6 mm punch biopsies (or four 4 mm punch biopsies) will be performed for research purposes, one (or two) of the affected area and one (or two) of a non-affected area (normal skin). Patients who have clinical resolution of their acute or chronic GVHD will undergo one additional 6 mm punch biopsy (or two additional 4 mm punch biopsies) of the previously affected area. This additional biopsy should occur within 10 cm of the previous affected area sample. With each skin biopsy, peripheral blood will be obtained by venipuncture or cannulation of an indwelling venous access device. Two optional skin biopsies. One on day 5-7 of treatment and one on day 28 from the start of treatment. | Procedure: Skin punch biopsy<br> <br> Procedure: Peripheral blood draw<br> <br> |
| Arm 2: Chronic skin GVHD<br>When clinically indicated, patients will undergo a skin biopsy to confirm a suspected diagnosis of acute or chronic GVHD, or to assess the status of their previously diagnosed acute or chronic GVHD. After the necessary samples are obtained for optimal medical care of the patient, two 6 mm punch biopsies (or four 4 mm punch biopsies) will be performed for research purposes, one (or two) of the affected area and one (or two) of a non-affected area (normal skin). Patients who have clinical resolution of their acute or chronic GVHD will undergo one additional 6 mm punch biopsy (or two additional 4 mm punch biopsies) of the previously affected area. This additional biopsy should occur within 10 cm of the previous affected area sample. With each skin biopsy, peripheral blood will be obtained by venipuncture or cannulation of an indwelling venous access device. Two optional skin biopsies. One on day 5-7 of treatment and one on day 28 from the start of treatment. | Procedure: Skin punch biopsy<br> <br> Procedure: Peripheral blood draw<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dendritic cell characteristics | Both GVHD affected and unaffected skin sections will be analyzed by immunostaining and the types of cells and strains of skin microbiota present will be analyzed The different isolated DCs will be activated by different stimuli and will be characterized by gene (DNA, RNA sequencing or arrays) and multicolor flow cytometry analysis. | Up to 2 years | 
| Antigen specific lymphocyte subset characteristics | Both GVHD affected and unaffected skin sections will be analyzed by immunostaining and the types of cells and strains of skin microbiota present will be analyzed CD4+ and CD8+ T cells or other lymphocyte populations will be isolated from peripheral blood by fluorescence activated cell sorting. The DC subsets purified from the skin tissue will be used to stimulate these T cell populations. This will be followed by thorough characterization of the charged T cell populations by a variety of methods. These will include assays to measure proliferation, gene array analysis cytokine secretion and other functions of the charged T cells. | Up to 2 years | 
| Genes and skin microbiota that correlate with dendritic cell function |  | Up to 2 years | 
| Potential treatment targets as measured by deep sequencing or microarray analysis |  | Up to 2 years |