Acute Graft-versus-host Disease, Acute GVHD, Chronic Graft-versus-host Disease, Chronic GVHD
Conditions
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.
Interventions
PROCEDURESkin punch biopsy
PROCEDUREPeripheral blood draw
Sponsors
Washington University School of Medicine
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREynav Klechevsky, Ph.D.
Washington University School of Medicine
Outcome results
None listed