Antibodies Targeting Surface Membrane Antigens in Patients with Chronic Graft-Versus-Host Disease

Kathy S. Wang, Haesook T. Kim, Sarah Nikiforow, Alexander T. Heubeck, Vincent T. Ho, John Koreth, Edwin P. Alyea, Philippe Armand, Bruce R. Blazar, Robert J. Soiffer, Joseph H. Antin, Corey S. Cutler and Jerome Ritz

Key points

  • Antibodies targeting cell membrane antigens in cGVHD.


Chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplant (HSCT) reflects a complex immune response resulting in chronic damage to multiple tissues. Previous studies indicated that donor B cells and the antibodies they produce play an important role in the development of cGVHD. To understand the pathogenic role of antibodies in cGVHD, we focused our studies on post-transplant production of IgG antibodies targeting cell surface antigens expressed in multiple cGVHD affected tissues, due to their potential functional impact on living cells in vivo. Using plate-bound cell membrane proteins as targets, we detected a significantly higher level of antibodies reactive with these membrane antigens in patients who developed cGVHD, compared to those who did not and healthy donors. Plasma reactive antibody levels increased significantly prior to the clinical diagnosis of cGVHD and were reduced following cGVHD therapies including prednisone, IL-2 or rituximab. Using cell-based immunoprecipitation with plasma from cGVHD patients and mass spectrometry, we identified 43 membrane proteins targeted by these antibodies. The presence of antibodies in cGVHD patients' plasma that specifically target 6 of these proteins was validated. Antibodies reactive with these 6 antigens were more frequently detected in patients with cGVHD compared to patients without cGVHD and healthy donors. These results indicate that antibodies that target membrane antigens of living cells frequently develop in cGVHD patients and further support a role for B cells and antibodies in the development of cGVHD.

  • Submitted August 14, 2017.
  • Accepted November 6, 2017.