High levels of B-cell activating factor in patients with active chronic graft-versus-host disease.
OBJECTIVE
Recent studies suggest that donor B cells as well as T cells contribute to immune pathology in patients with chronic graft-versus-host disease (GVHD). B-cell activating factor (BAFF) promotes survival and differentiation of activated B cells. Thus, we tested whether BAFF correlated with chronic GVHD disease activity and time of onset after allogeneic hematopoietic stem cell transplantation (HSCT).


METHODS
Patients who had undergone allogeneic HSCT between 1994 and 2005 for hematologic malignancies were studied. ELISA was used to measure plasma BAFF levels and flow cytometry was used to assess BAFF receptor expression on B cells in patients with or without chronic GVHD.


RESULTS
In 104 patients, BAFF levels were significantly higher in patients with active chronic GVHD compared with those without disease (P = 0.02 and 0.0004, respectively). Treatment with high-dose prednisone (>or=30 mg/d) was associated with reduced BAFF levels in patients with active chronic GVHD (P = 0.0005). Serial studies in 24 patients showed that BAFF levels were high in the first 3 months after HSCT but subsequently decreased in 13 patients who never developed chronic GVHD. In contrast, BAFF levels remained elevated in 11 patients who developed chronic GVHD. Six-month BAFF levels >or=10 ng/mL were strongly associated with subsequent development of chronic GVHD (P < 0.0001). Following transplant, plasma BAFF levels correlated inversely with BAFF receptor expression on B cells (P = 0.01), suggesting that soluble BAFF affected B cells through this receptor.


CONCLUSIONS
These results suggest that elevated BAFF levels contribute to B-cell activation in patients with active chronic GVHD.
Sarantopoulos
Stefanie
S
Division of Hematologic Malignancies and Department of Medical Oncolog, Dana-Farber Cancer Institute and Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Stevenson
Kristen E
KE
Kim
Haesook T
HT
Bhuiya
Nazmim S
NS
Cutler
Corey S
CS
Soiffer
Robert J
RJ
Antin
Joseph H
JH
Ritz
Jerome
J
D000208:Acute Disease; D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000097:blood* / Q000502:physiology; D002454:Cell Differentiation; D002908:Chronic Disease; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006086:Graft vs Host Disease / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000628:therapy*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D053264:B-Cell Activating Factor