This article appeared in the June 2018 issue of ASBMT eNews. Download the full issue in PDF format here
Study Looks at Skin GVHD Impact and Treatment
Graft-versus-host disease (GVHD) targets Lgr5+ hair follicle stem cells (HFSCs), and topical ruxolitinib protects skin stem cells and maintains skin homeostasis in GVHD, reports a study appearing in Blood. Using mice, researchers discovered that GVHD reduced Lgr5+ HFSCs in association with impaired hair regeneration and skin wound healing after transplantation. Topical corticosteroids damaged HFSCs and failed to improve skin homeostasis, but ruxolitinib improved skin GVHD, protected Lgr5+ HFSCs and restored hair regeneration and wound healing. Read More
miR-17-92 and Its Role in Chronic GVHD
A Blood study reports that microRNA-17-92 (miR-17-92) plays a key role in the development of chronic graft-versus-host disease (GVHD). The study was conducted to determine if miR-17-92 regulates T- and B-cell responses in chronic GVHD. Researchers discovered donor T and B cells are necessary for generating scleroderma and bronchiolitis obliterans in chronic GVHD. In T cells, miR-17-92 expression improves pathogenic T helper 1 (Th1) and Th17 cell differentiation and generates follicular Th cells, germinal center (GC) B cells and plasma cells. In B cells, miR-17-92 expression produces autoantibodies and deposits immunoglobulin G in the skin. The researchers also evaluated a translational approach using antagomirs specific for either miR-17 or miR-19. Systemic administration of anti-miR-17 eliminated clinical manifestations and proteinuria incidence in recipients by inhibiting donor lymphocyte expansion, B-cell activation and GC responses. In addition, miR-17 blockade improved skin damage by reducing Th17 differentiation. These study results led researchers to conclude that miR-17-92 is required for differentiation and function of T and B cells and pharmacological inhibition of miR-17 may prevent chronic GVHD. Read More
SCID-X1 Treatment Treats Disease and Eliminates Need for Conditioning
Intravenous administration of foamy virus (FV) vectors effectively treats X-linked severe combined immunodeficiency disease (SCID-X1) in dogs, eliminating the need for conditioning, according to a study published in Blood Advances. Researchers demonstrated improved efficacy of the in vivo gene therapy by mobilization with granulocyte colony-stimulating factor and AMD3100 before injection of an optimized FV vector incorporating the human phosphoglycerate kinase enhancerless promoter. Mobilization prior to FV vector administration accelerated kinetics of CD3+ lymphocyte recovery, promoted thymopoiesis and increased immune clonal diversity. Gene-corrected T lymphocytes showed a normal CD4:CD8 ratio and a broad T-cell receptor repertoire and displayed restored ƴC-dependent signaling function. Treated dogs had normal primary and secondary antibody responses to bacteriophage immunization and evidence for immunoglobulin class switching. Read More