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

NCT02611180 | Active Not Recruiting

• 1 other identifier: 201405065
• Study Type: observational
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Graft-versus-host Disease; Acute Graft-versus-host Disease; Acute GVHD; Chronic GVHD

Outcome Measures

Primary Outcomes (4)

• 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

Study Arms (2)

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.

Procedure: Skin punch biopsy; Procedure: Peripheral blood draw

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.

Procedure: Skin punch biopsy; Procedure: Peripheral blood draw

Interventions

Skin punch biopsy PROCEDURE

Arm 1: Acute skin GVHD; Arm 2: Chronic skin GVHD

Peripheral blood draw PROCEDURE

Arm 1: Acute skin GVHD; Arm 2: Chronic skin GVHD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with current or suspected acute or chronic GVHD of the skin

You may qualify if:

• 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

You may not qualify if:

• Known infection with Hepatitis B or C, HTLV, or HIV
• Pregnant females

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Biospecimen

Retention: SAMPLES WITH DNA

Skin samples and blood samples

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Officials

• Eynav Klechevsky, Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2015
• First Posted: November 20, 2015
• Study Start: April 30, 2015
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)