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Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease.

Abstract
Chronic graft-versus-host disease (cGVHD) causes significant morbidity and mortality in patients otherwise cured of malignancy after hematopoietic stem cell transplantation (HSCT). The presence of alloantibodies and high plasma B cell-activating factor (BAFF) levels in patients with cGVHD suggest that B cells play a role in disease pathogenesis. We performed detailed phenotypic and functional analyses of peripheral B cells in 82 patients after HSCT. Patients with cGVHD had significantly higher BAFF/B-cell ratios compared with patients without cGVHD or healthy donors. In cGVHD, increasing BAFF concentrations correlated with increased numbers of circulating pre-germinal center (GC) B cells and post-GC "plasmablast-like" cells, suggesting in vivo BAFF dependence of these 2 CD27(+) B-cell subsets. Circulating CD27(+) B cells in cGVHD comprised in vivo activated B cells capable of IgG production without requiring additional antigen stimulation. Serial studies revealed that patients who subsequently developed cGVHD had delayed reconstitution of naive B cells despite persistent BAFF elevation as well as proportional increase in CD27(+) B cells in the first year after HSCT. These studies delineate specific abnormalities of B-cell homeostasis in patients with cGVHD and suggest that BAFF targeting agents may be useful in this disease.
AuthorsStefanie Sarantopoulos, Kristen E Stevenson, Haesook T Kim, Corey S Cutler, Nazmim S Bhuiya, Michael Schowalter, Vincent T Ho, Edwin P Alyea, John Koreth, Bruce R Blazar, Robert J Soiffer, Joseph H Antin, Jerome Ritz
JournalBlood (Blood) Vol. 113 Issue 16 Pg. 3865-74 (Apr 16 2009) ISSN: 1528-0020 [Electronic] United States
PMID19168788 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD27
  • B-Cell Activating Factor
  • Immunoglobulin G
  • Isoantibodies
  • TNFSF13B protein, human
Topics
  • Adult
  • Aged
  • Antigens, CD27 (immunology, metabolism)
  • B-Cell Activating Factor (blood, immunology)
  • B-Lymphocyte Subsets (immunology, pathology)
  • Chronic Disease
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease (blood, immunology, mortality, pathology, therapy)
  • Hematologic Neoplasms (immunology, mortality, pathology, therapy)
  • Hematopoietic Stem Cell Transplantation
  • Homeostasis (immunology)
  • Humans
  • Immunoglobulin G (blood, immunology)
  • Isoantibodies (blood, immunology)
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transplantation, Homologous

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