Project description:RATIONALE: Beclomethasone may be an effective treatment for graft-versus-host disease. PURPOSE: Phase I/II trial to study the effectiveness of beclomethasone in treating patients who have graft-versus-host disease of the esophagus, stomach, small intestine, or colon.

| 2005776 | ecrin-mdr-crc

Distinctive Transcriptional and Microbial Signature in Cutaneous Acute Graft-vs-Host-Disease

Project description:Distinctive Transcriptional and Microbial Signature in Cutaneous Acute Graft-vs-Host-Disease

| PRJNA1098051 | ENA

Distinctive Transcriptional and Microbial Signature in Cutaneous Acute Graft-vs-Host-Disease

Project description:Skin acute graft-vs-host disease (aGVHD) is often the first manifestation of GVHD, yet very few preclinical and clinical studies have focused on this target organ, leaving a critical information gap in the pathophysiology of GVHD. We hypothesized that analysis of host gene expression and microbiome profiling could yield novel insights into the molecular and immunologic mechanisms underlying skin GVHD. Our objectives were to determine the differential host gene expression and microbiome profile of human skin aGVHD samples compared to normal skin, and aGVHD corticosteroid responders to non-responders. We performed RNA-Sequencing on lower arm biopsies from 45 patients compared to 10 healthy controls. Our findings suggest a distinctive transcriptional signature of cutaneous aGVHD, that could identify potentially actionable targets for prevention or treatment of corticosteroid refractory disease. Our analysis suggests a key role of dendritic cells and macrophages, potentially mediated by differential expression of MIF, in the development of cutaneous aGVHD and corticosteroid responsiveness. Additionally, we describe a unique microbial signature in cutaneous aGVHD that includes skin microbes not previously described in this population.

2024-04-12 | GSE263557 | GEO

CIDR: Collaborative Study on the Genetics of Alcoholism (COGA)

Project description:CIDR: Collaborative Study on the Genetics of Alcoholism (COGA)

| PRJNA75781 | ENA

Microbiota dictate T cell clonal selection to augment graft-vs-host disease after stem cell transplantation

Project description:Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-MHC complexes, though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient TCR frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4 T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigen presented by gastrointestinal epithelium during an alloreactive response. The microbiota thus serves as a source of cognate antigen that contributes to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics.

2024-06-03 | GSE267178 | GEO

Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies

Project description:This phase II trial studies how well cyclophosphamide works in preventing chronic graft-versus-host disease after allogeneic peripheral blood stem cell transplant in patients with hematological malignancies. Giving chemotherapy and total-body irradiation before transplantation helps stop the growth of cancer cells and prevents the patient’s immune system from rejecting the donor’s stem cells. Healthy stem cells from a donor that are infused into the patient help the patient’s bone marrow make blood cells; red blood cells, white blood cells, and platelets. Sometimes, however, the transplanted donor cells can cause an immune response against the body’s normal cells, which is called graft-versus-host disease (GVHD). Giving cyclophosphamide after transplant may prevent this from happening or may make chronic GVHD less severe.

| 2112331 | ecrin-mdr-crc

Microbiota dictate T cell clonal selection to augment graft-vs-host disease after stem cell transplantation

Project description:Microbiota dictate T cell clonal selection to augment graft-vs-host disease after stem cell transplantation

| PRJNA1110174 | ENA