Work

Elevated B cell activating factor (BAFF) in patient plasma after allogeneic stem cell transplantation is a potential biomarker for chronic graft versus host disease

Year: 2006

Type: article

Abstract: Previous studies have identified a highly significant correlation between specific antibody responses directed against recipient H-Y minor histocompatibility antigens and the development of chronic graft versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). These findings suggest that donor B cells play a role in the development of cGVHD and clinical trials utilizing anti-CD20 monoclonal antibody, rituximab, have demonstrated clinical improvement in some patients with active resistant cGVHD. B cell activating factor, BAFF, is a member of the TNF cytokine family that binds to one of three cell surface receptors on B cells. Activation of these B cell receptors by antigen and BAFF results in rapid induction of proliferation and differentiation of germinal center B cells into either Ig-secreting cells or memory B cells. The finding that elevated BAFF levels in patients with autoimmune diseases are associated with disease severity and autoantibody production has led to clinical trials using anti-BAFF monoclonal antibody in these diseases. To test whether BAFF contributes to the activation of B cells in patients with cGVHD, we employed a sandwich ELISA to measure soluble BAFF in plasma from 27 patients after allogeneic HSCT. Mean BAFF levels for extensive (n = 8), limited (n = 8), resolved (n = 6) or no (n = 5) cGVHD groups were: 7.3 ng/ml, 5.37 ng/ml, 3.92 ng/ml and 2.02 ng/ml, respectively. The differences between the extensive or limited groups versus the no cGVHD group were statistically significant (each P = .03) suggesting that BAFF levels corresponded with cGVHD activity. B cell subsets in peripheral blood were also examined by flow cytometry to identify circulating memory B cells. Of four cGVHD patients analyzed thus far, individuals with active disease and high BAFF levels also had high numbers of CD27+ memory B cells in peripheral blood compared to patients with resolved cGVHD and low BAFF levels. Ongoing prospective, serial assessment of BAFF levels and B cell phenotype in larger numbers of patients will extend these results. We propose that BAFF may serve as a new biomarker for cGVHD, specifically identifying patients with active disease. If further studies identify a pathologic role for increased BAFF in cGVHD, anti-BAFF monoclonal antibodies may provide a new therapeutic approach for this serious complication of allogeneic HSCT.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2005.11.177