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

Publication ,  Journal Article
Sarantopoulos, S; Stevenson, KE; Kim, HT; Cutler, CS; Bhuiya, NS; Schowalter, M; Ho, VT; Alyea, EP; Koreth, J; Blazar, BR; Soiffer, RJ ...
Published in: Blood
April 16, 2009

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.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

April 16, 2009

Volume

113

Issue

16

Start / End Page

3865 / 3874

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Transplantation, Homologous
  • Retrospective Studies
  • Middle Aged
  • Male
  • Isoantibodies
  • Immunology
  • Immunoglobulin G
  • Humans
  • Homeostasis
 

Citation

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Sarantopoulos, S., Stevenson, K. E., Kim, H. T., Cutler, C. S., Bhuiya, N. S., Schowalter, M., … Ritz, J. (2009). Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease. Blood, 113(16), 3865–3874. https://doi.org/10.1182/blood-2008-09-177840
Sarantopoulos, Stefanie, Kristen E. Stevenson, Haesook T. Kim, Corey S. Cutler, Nazmim S. Bhuiya, Michael Schowalter, Vincent T. Ho, et al. “Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease.Blood 113, no. 16 (April 16, 2009): 3865–74. https://doi.org/10.1182/blood-2008-09-177840.
Sarantopoulos S, Stevenson KE, Kim HT, Cutler CS, Bhuiya NS, Schowalter M, et al. Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease. Blood. 2009 Apr 16;113(16):3865–74.
Sarantopoulos, Stefanie, et al. “Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease.Blood, vol. 113, no. 16, Apr. 2009, pp. 3865–74. Pubmed, doi:10.1182/blood-2008-09-177840.
Sarantopoulos S, Stevenson KE, Kim HT, Cutler CS, Bhuiya NS, Schowalter M, Ho VT, Alyea EP, Koreth J, Blazar BR, Soiffer RJ, Antin JH, Ritz J. Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease. Blood. 2009 Apr 16;113(16):3865–3874.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

April 16, 2009

Volume

113

Issue

16

Start / End Page

3865 / 3874

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Transplantation, Homologous
  • Retrospective Studies
  • Middle Aged
  • Male
  • Isoantibodies
  • Immunology
  • Immunoglobulin G
  • Humans
  • Homeostasis