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Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-03-0984.
Submitted March 31, 2003
Accepted September 14, 2003
Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in normal female donors
David B Miklos, Haesook T Kim, Emmanuel Zorn, Ephraim P Hochberg, Luxuan Guo, Alex Mattes-Ritz, Sebastien Viatte, Robert J Soiffer, Joseph H Antin, and Jerome Ritz*
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Department of Biostatistical Science, Dana-Farber Cancer Institute, Boston, MA, USA
* Corresponding author; email: Jerome_Ritz{at}DFCI.Harvard.edu.
Minor histocompatibility antigens (mHA) recognized by donor T cells play a central role as immunologic targets of graft versus host disease (GVHD) and graft versus leukemia after allogeneic hematopoietic stem cell transplantation (HSCT). Males who have undergone sex-mismatched allogeneic HSCT are at high risk for GVHD because of immune responses directed against mHA encoded by genes on the Y-chromosome (termed H-Y antigens). We hypothesized that the immunogenicity of mHA results in a coordinated response involving B cells as well as T cells. To test this, we measured antibody responses to a well-characterized H-Y antigen, DBY and its homologue DBX, in 150 HSCT patients. Using western blot and ELISA, 50% of male patients who received stem cell grafts from female donors developed antibody responses to recombinant DBY protein. Antibodies to DBY were also detected in 17% of normal females, but not in normal males. Antibody responses were primarily directed against areas of amino acid disparity between DBY and DBX. These studies demonstrate that the immune response to mHA includes the generation of specific antibodies and suggests that the serologic response to these antigens may be useful in the identification of new mHA.
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