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.
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: David B Miklos; Haesook T Kim; Emmanuel Zorn; Ephraim P Hochberg; Luxuan Guo; Alex Mattes-Ritz; Sebastien Viatte; Robert J Soiffer; Joseph H Antin; Jerome Ritz Journal: Blood Date: 2003-09-25 Impact factor: 22.113
Authors: Voravit Ratanatharathorn; Lois Ayash; Christopher Reynolds; Samuel Silver; Pavan Reddy; Michael Becker; James L M Ferrara; Joseph P Uberti Journal: Biol Blood Marrow Transplant Date: 2003-08 Impact factor: 5.742
Authors: Jonathan C W Edwards; Leszek Szczepanski; Jacek Szechinski; Anna Filipowicz-Sosnowska; Paul Emery; David R Close; Randall M Stevens; Tim Shaw Journal: N Engl J Med Date: 2004-06-17 Impact factor: 91.245
Authors: Emmanuel Zorn; David B Miklos; Blair H Floyd; Alex Mattes-Ritz; Luxuan Guo; Robert J Soiffer; Joseph H Antin; Jerome Ritz Journal: J Exp Med Date: 2004-04-19 Impact factor: 14.307
Authors: Leonid Gorelik; Kevin Gilbride; Max Dobles; Susan L Kalled; Daniel Zandman; Martin L Scott Journal: J Exp Med Date: 2003-09-15 Impact factor: 14.307
Authors: Zoya Kuzmina; Verena Gounden; Lauren Curtis; Daniele Avila; Tiffani Taylor Rnp; Judy Baruffaldi; Edward W Cowen; Haley B Naik; Sarfaraz A Hasni; Jacqueline W Mays; Sandra Mitchell; Kristin Baird; Seth M Steinberg; Steven Z Pavletic Journal: Am J Hematol Date: 2014-11-24 Impact factor: 10.047
Authors: Mathangi Srinivasan; Ryan Flynn; Andrew Price; Ann Ranger; Jeffrey L Browning; Patricia A Taylor; Jerome Ritz; Joseph H Antin; William J Murphy; Leo Luznik; Mark J Shlomchik; Angela Panoskaltsis-Mortari; Bruce R Blazar Journal: Blood Date: 2011-11-09 Impact factor: 22.113
Authors: Bita Sahaf; Yang Yang; Sally Arai; Leonard A Herzenberg; Leonore A Herzenberg; David B Miklos Journal: Proc Natl Acad Sci U S A Date: 2013-02-04 Impact factor: 11.205
Authors: Frances T Hakim; Sarfraz Memon; Ping Jin; Matin M Imanguli; Huan Wang; Najibah Rehman; Xiao-Yi Yan; Jeremy Rose; Jacqueline W Mays; Susan Dhamala; Veena Kapoor; William Telford; John Dickinson; Sean Davis; David Halverson; Haley B Naik; Kristin Baird; Daniel Fowler; David Stroncek; Edward W Cowen; Steven Z Pavletic; Ronald E Gress Journal: J Immunol Date: 2016-09-30 Impact factor: 5.422
Authors: Jonathan C Poe; Wei Jia; Julie A Di Paolo; Nancy J Reyes; Ji Yun Kim; Hsuan Su; John S Sundy; Adela R Cardones; Victor L Perez; Benny J Chen; Nelson J Chao; Diana M Cardona; Daniel R Saban; Stefanie Sarantopoulos Journal: JCI Insight Date: 2018-10-04