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

Recruiting

• Conditions: Chronic Graft-versus-host Disease; Acute Graft-versus-host Disease; Chronic GVHD; Acute GVHD
• Interventions: Procedure: Skin punch biopsy; Procedure: Peripheral blood draw

• Registration Number: NCT02611180
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04-30
• Study First Submitted: 2015-11-12
• Study First Submitted QC: 2015-11-18
• Study First Posted: 2015-11-20
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-13
• Primary Completion: 2026-04-30
• Study Completion: 2026-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Arm 2: Chronic skin GVHD	Peripheral blood draw	* 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.
Arm 1: Acute skin GVHD	Skin punch biopsy	* 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.
Arm 2: Chronic skin GVHD	Skin punch biopsy	* 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.
Arm 1: Acute skin GVHD	Peripheral blood draw	* 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.

Primary Outcome Measures

Name	Time	Method
Dendritic cell characteristics	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	Up to 2 years
Potential treatment targets as measured by deep sequencing or microarray analysis	Up to 2 years
Antigen specific lymphocyte subset characteristics	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.

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States