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Bone marrow T-cell infiltration during acute GVHD is associated with delayed B-cell recovery and function after HSCT

Item Type:Article
Title:Bone marrow T-cell infiltration during acute GVHD is associated with delayed B-cell recovery and function after HSCT
Creators Name:Mensen, A. and Jöhrens, K. and Anagnostopoulos, I. and Demski, S. and Oey, M. and Stroux, A. and Hemmati, P. and Westermann, J. and Blau, O. and Wittenbecher, F. and Movassaghi, K. and Szyska, M. and Thomas, S. and Dörken, B. and Scheibenbogen, C. and Arnold, R. and Na, I.K.
Abstract:B-cell immune dysfunction contributes to the risk of severe infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Delayed B-cell regeneration is found in patients with systemic graft-versus-host disease (GVHD) and is often accompanied by bone marrow (BM) suppression. Little is known about human BM GVHD. We analyzed the reconstitution kinetics of B-cell subsets in adult leukemic patients within 6 months after allo-HSCT. B-cell deficiency already existed before transplant and was aggravated after transplant. Onset of B-cell reconstitution characterized by transitional B-cell recovery occurred either early (months 2-3) or late (from month 6 on) and correlated highly positively with reverse transcription-polymerase chain reaction quantified numbers of kappa-deleting recombination excision circles (KRECs). Delayed recovery was associated with systemic acute GVHD and full-intensity conditioning therapy. Histological analysis of BM trephines revealed increased T-cell infiltration in late recovering patients, which was associated with reduced numbers of osteoblasts. Functionally, late recovering patients displayed less pneumococcal polysaccharide-specific immunoglobin M-producing B cells on ex vivo B-cell activation than early recovering patients. Our results provide evidence for acute BM GVHD in allo-HSCT patients with infiltrating donor T cells and osteoblast destruction. This is associated with delayed B-cell reconstitution and impaired antibody response. Herein, KREC appears suitable to monitor BM B-cell output after transplant.
Keywords:Acute Disease, Allografts, B-Lymphocyte Subsets, Bone Marrow, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Light Chain B-Lymphocyte Gene Rearrangement, Lymphocyte Activation, Osteoblasts, T-Lymphocytes, Time Factors, Young Adult
Publisher:American Society of Hematology
Page Range:963-972
Date:7 August 2014
Official Publication:https://doi.org/10.1182/blood-2013-11-539031
PubMed:View item in PubMed

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