title: Recovery of B-cell homeostasis after rituximab in chronic graft-versus-host disease.
abstract: Investigation of the effects of rituximab (anti-CD20) on B-cell-activating factor of the tumor necrosis factor family (BAFF) and B cells would better define the significance of B-cell homeostasis in chronic graft-versus-host disease (cGVHD) pathophysiology. We studied 20 cGVHD patients at a median of 25 months after rituximab treatment when most patients had recovered total B-cell numbers. A total of 55% of patients had stable/improved cGVHD, and total B-cell numbers in these patients were significantly higher compared with rituximab-unresponsive patients. Although total B-cell number did not differ significantly between cGVHD groups before rituximab, there was a proportional increase in B-cell precursors in patients who later had stable/improved cGVHD. After rituximab, BAFF levels increased in all patients. Coincident with B-cell recovery in the stable/improved group, BAFF/B-cell ratios and CD27(+) B-cell frequencies decreased significantly. The peripheral B-cell pool in stable/improved cGVHD patients was largely composed of naive IgD(+) B cells. By contrast, rituximab-unresponsive cGVHD patients had persistent elevation of BAFF and a predominance of circulating B cells possessing an activated BAFF-R(Lo)CD20(Lo) cell surface phenotype. Thus, naive B-cell reconstitution and decreased BAFF/B-cell ratios were associated with clinical response after rituximab in cGVHD. Our findings begin to delineate B-cell homeostatic mechanisms important for human immune tolerance.
authors.affiliation: University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA. stefanie_sarantopoulos@med.unc.edu
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sarantopoulos
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Stevenson
authors.forename: Haesook T
authors.initials: HT
authors.lastname: Kim
authors.forename: Whitney S
authors.initials: WS
authors.lastname: Washel
authors.forename: Nazmim S
authors.initials: NS
authors.lastname: Bhuiya
authors.forename: Corey S
authors.initials: CS
authors.lastname: Cutler
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood; D053264:B-Cell Activating Factor / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D053264:B-Cell Activating Factor; C035356:SS-A antibodies; C505719:TNFSF13B protein, human; D000069283:Rituximab