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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., Jöhrens, K., Anagnostopoulos, I., Demski, S., Oey, M., Stroux, A., Hemmati, P., Westermann, J., Blau, O., Wittenbecher, F., Movassaghi, K., Szyska, M., Thomas, S., Dörken, B., Scheibenbogen, C., 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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