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

Stefanie 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

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201 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3865-3874
Number of pages10
JournalBlood
Volume113
Issue number16
DOIs
StatePublished - Nov 17 2009

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    Sarantopoulos, S., Stevenson, K. E., Kim, H. T., Cutler, C. S., Bhuiya, N. S., Schowalter, M., Ho, V. T., Alyea, E. P., Koreth, J., Blazar, B. R., Soiffer, R. J., Antin, J. H., & 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