Bone marrow T-cell infiltration during acute GVHD is associated with delayed B-cell recovery and function after HSCT.
Title | Bone marrow T-cell infiltration during acute GVHD is associated with delayed B-cell recovery and function after HSCT. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | 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., & Na I-K. |
Journal | Blood |
Volume | 124 |
Issue | 6 |
Pagination | 963-72 |
Date Published | 2014 Aug 7 |
ISSN | 1528-0020 |
Keywords | Acute Disease, Adult, Aged, Allografts, B-Lymphocyte Subsets, Bone Marrow, Female, Gene Rearrangement, B-Lymphocyte, Light Chain, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Lymphocyte Activation, Male, Middle Aged, Osteoblasts, T-Lymphocytes, Time Factors, Young Adult |
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 κ-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. |
DOI | 10.1182/blood-2013-11-539031 |
Alternate Journal | Blood |
PubMed ID | 24833353 |