(WASHINGTON) – Welcome to “This Week in Blood,” a weekly snapshot of the hottest studies from each week’s issue of Blood, the official journal of the American Society of Hematology (ASH), hand-picked by Blood Editor-in-Chief Bob Löwenberg, MD, and Deputy Editor Nancy Berliner, MD. If you would like a PDF copy of any of the manuscripts highlighted below or would like to request an interview with the author, please email firstname.lastname@example.org.
Multicenter study of banked third-party virus-specific T-cells to treat severe viral infections after hematopoietic stem cell transplantation, Leen et al.
This week’s Plenary Paper reports the first multicenter trial to evaluate the use of third-party virus-specific T cells as potential treatment for patients with stem-cell-transplant-related intractable viral infections. While previous studies have used these lines for prevention, this is the first and largest trial to evaluate their efficacy as a treatment of established active disease. Utilizing “off the shelf” T cell lines with variable human leukocyte antigen mismatch, researchers observed the T cell lines were effective against more than 70 percent of cases of Epstein-Barr virus, cytomegalovirus, and adenovirus, with very few cases of graft-versus-host disease (GVHD). As highlighted in an accompanying “Inside Blood” article, however, patients enrolled in this trial were carefully selected: they did not have active GVHD, had not undergone T-cell depletion, and were not taking high doses of prednisone. Whether these lines will work as well in more immunocompromised patients remains to be determined in future trials. Nevertheless, these results represent a major advance in the treatment of life-threatening viral infection following stem cell transplant.
Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8+ T cells and dendritic cells, Terrell et al.
Perforin deficiency is the leading cause of familial hemophagocytic lymphohistiocytosis (HLH). While perforin deficiency is known to disrupt immune responsiveness, causing increased natural killer and T-cell activation with release of cytokines and downstream macrophage activation, the mechanism by which perforin exercises control over immune activation is unknown. In this week’s issue of Blood, Terrell and colleagues shed light on this process using a mouse model of perforin deficiency. They demonstrate that persistent antigen stimulation leading to HLH is driven by a small number of dendritic cells and that perforin-dependent elimination of these rare cells is required to control the level of antigen stimulation and immune activation. Depletion of these rare dendritic cells prevents the development of HLH and may offer new avenues of exploration to improve therapy of this fatal disorder.
The C-type lectin receptor CLEC4M binds, internalizes and clears von Willebrand factor and contributes to the variation in plasma von Willebrand factor levels, Rydz et al.
In this week’s issue of Blood, Rydz and colleagues explore the basis for the significant association between genetic variation in/near the C-type lectin domain family 4 member M (CLEC4M) and plasma von Willebrand Factor (VWF) levels in normal individuals. They demonstrate that CLEC4M, a lectin receptor with a polymorphic extracellular neck region possessing a variable number of tandem repeats (VNTR), binds to VWF, leading to its internalization within cells. Further, Rydz and colleagues demonstrate that polymorphisms of the VNTR region lead to variable binding interaction with VWF, thereby explaining variations in the level of extracellular VWF. This observation may begin to explain the wide range of VWF plasma levels in normal individuals as well as the variable plasma VWF levels within relatives of patients with VWD.
Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field of hematology, is available weekly in print and online. Blood is the official journal of the American Society of Hematology (ASH) (www.hematology.org), the world’s largest professional society concerned with the causes and treatment of blood disorders.
ASH’s mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology.
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