Protein Implicated in Aberrant B-cell Survival in Transplant Disease

Ex vivo study finds that B-cells from patients with chronic graft vs. host disease (cGVHD) are in a heightened metabolic state and are resistant to apoptosis compared to patients without cGVHD, and leads to identification of a key candidate target for development of more effective drug therapies.

The research team, primarily from University of North Carolina’s Lineberger Comprehensive Cancer Center (UNC Lineberger; Chapel Hill, NC, USA), performed ex vivo analyses of peripheral B cells from 51 patients who either had or did not have active cGVHD and were greater than one year from the time of allogeneic hematopoietic stem cell (HSCT) transplantation. In addition to the finding of the aberrantly sustained activation of the B-cells from patients with cGVHD, an investigation into the mechanisms involved in this process led to the implication of a mechanistic link between this abnormal B-cell survival and the TNF family member signaling protein called BAFF, thus identifying BAFF as having an important role in the pathogenesis of cGVHD.

For patients who received bone marrow or stem cells, it is estimated that 40%-70% may experience chronic GVHD.

“Steroids are currently our only standard treatment for chronic GVHD and they are often not effective,” noted senior author Stefanie Sarantopoulos, MD, PhD, assistant professor in the division of hematology/oncology and the departments of microbiology and immunology at the UNC School of Medicine. This study offers BAFF and the BAFF-mediated signaling pathways that contribute to this “revved up” B-cell activity as potentially suitable sources of novel therapeutic targets for chronic GVHD patients.

The study was published August 15, 2012, in the journal Blood.

Related Links:
University of North Carolina’s Lineberger Comprehensive Cancer Center