High levels of B-cell activating factor in patients with active chronic graft-versus-host disease.

Abstract

PURPOSE:

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).

EXPERIMENTAL DESIGN:

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.

CONCLUSION:

These results suggest that elevated BAFF levels contribute to B-cell activation in patients with active chronic GVHD.

• Authors: Stefanie Sarantopoulos, Kristen E Stevenson, Haesook T Kim, Nazmim S Bhuiya, Corey S Cutler, Robert J Soiffer, Joseph H Antin, Jerome Ritz
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 20 Pg. 6107-14 (Oct 15 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17947475 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• B-Cell Activating Factor

Topics

• Acute Disease
• Adult
• Aged
• B-Cell Activating Factor (blood, physiology)
• Cell Differentiation
• Chronic Disease
• Female
• Gene Expression Regulation, Neoplastic
• Graft vs Host Disease (metabolism)
• Hematopoietic Stem Cell Transplantation
• Humans
• Lymphocyte Activation
• Male
• Middle Aged
• Neoplasms (blood, therapy)
• Transplantation, Homologous
• Treatment Outcome