This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sarantopoulos, S. Articles by Ritz, J. Search for Related Content PubMed PubMed Citation Articles by Sarantopoulos, S. Articles by Ritz, J.

High Levels of B-Cell Activating Factor in Patients with Active Chronic Graft-Versus-Host Disease

Authors' Affiliations: ¹ Division of Hematologic Malignancies and Department of Medical Oncology and ² Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and ³ Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts

Requests for reprints: Jerome Ritz, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115. Phone: 617-632-3465; Fax: 617-632-5167; E-mail: jerome_ritz{at}dfci.harvard.edu.

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 (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 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.