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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic GVHD; Acute Graft-versus-host Disease; Chronic Graft-versus-host Disease; Acute GVHD
• Intervention / Treatment: Procedure: Skin punch biopsy; Procedure: Peripheral blood draw

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Eynav Klechevsky, Ph.D.; Phone Number: 314-286-0897; Email: eklechevsky@wustl.edu
• Study Contact Backup: Name: Caroline Bumb; Phone Number: 314-362-7249; Email: cbumb@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Geoffrey Uy, M.D.
      • Sub-Investigator: John F DiPersio, M.D., Ph.D.
      • Sub-Investigator: Armin Ghobadi, M.D.
      • Sub-Investigator: Peter Westervelt, M.D., Ph.D.
      • Sub-Investigator: Camille Abboud, M.D.
      • Sub-Investigator: Amanda Cashen, M.D.
      • Sub-Investigator: Keith Stockerl-Goldstein, M.D.
      • Sub-Investigator: Ravi Vij, M.D.
      • Sub-Investigator: Todd Fehniger, M.D., Ph.D.
      • Sub-Investigator: Iskra Pusic, M.D.
      • Sub-Investigator: John Welch, M.D., Ph.D.
      • Sub-Investigator: Mark Schroeder, M.D.
      • Sub-Investigator: Amy Musiek, M.D.
      • Sub-Investigator: Matthew Walter, M.D.
      • Contact: Eynav Klechevsky, Ph.D.; Phone Number: 314-286-0897; Email: eklechevsky@wustl.edu
      • Contact: Caroline Bumb; Phone Number: 314-362-7249; Email: cbumb@wustl.edu
      • Principal Investigator: Eynav Klechevsky, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Eynav Klechevsky, Ph.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2015
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): April 30, 2025

Study Registration Dates

• First Submitted: November 12, 2015
• First Submitted That Met QC Criteria: November 18, 2015
• First Posted (Estimated): November 20, 2015

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Bronchiolitis Obliterans; Bronchiolitis; Organizing Pneumonia; Graft vs Host Disease; Bronchiolitis Obliterans Syndrome
• Other Study ID Numbers: 201405065

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No