Analysis of Dendritic Cells in Patients With Acute or Chronic Skin Graft Versus Host Disease
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Dendritic cell characteristics
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Known infection with Hepatitis B or C, HTLV, or HIV
- •Pregnant females
研究组 & 干预措施
Arm 1: Acute skin GVHD
- 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.
干预措施: Skin punch biopsy (Procedure)
Arm 1: Acute skin GVHD
- 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.
干预措施: Peripheral blood draw (Procedure)
Arm 2: Chronic skin GVHD
- 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.
干预措施: Skin punch biopsy (Procedure)
Arm 2: Chronic skin GVHD
- 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.
干预措施: Peripheral blood draw (Procedure)
结局指标
主要结局
Dendritic cell characteristics
时间窗: Up to 2 years
* 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.
Genes and skin microbiota that correlate with dendritic cell function
时间窗: Up to 2 years
Potential treatment targets as measured by deep sequencing or microarray analysis
时间窗: Up to 2 years
Antigen specific lymphocyte subset characteristics
时间窗: Up to 2 years
* 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.
次要结局
未报告次要终点