Antibody Barriers Project

A major project of the Transplant Immunology Program is advancing the science of transplantation to overcome antibody barriers to immediate and long-term transplant success, such as kidney transplantation across blood group and positive crossmatch barriers.

One example of these barriers is the action of antibodies against human leukocyte antigen, proteins found on the surface of cells responsible for regulation of the immune system. Cells displaying different varieties of human leukocyte antigen are seen as nonself or foreign and trigger an immune response against them. In the content of transplanted tissue, this can result in rejection and is a major cause of both early and late graft damage.

Many transplant candidates develop antibodies against human leukocyte antigen due to past exposure to foreign forms of this antigen from sources including pregnancy, blood transfusion or a previous (failed) kidney transplant. These antibodies can be a major barrier to transplant success, with 1 in 3 kidney transplant candidates having antibodies at the time of transplant that may attack the transplanted organ.

Kidney transplantation is usually not performed if the potential donor has a different blood type than the recipient or if the recipient is shown to have pre-existing antibodies that recognize donor cells (a "positive crossmatch"). In these circumstances there is a high risk that the transplanted kidney would be quickly destroyed as a result of antibody binding.

Antibodies against human leukocyte antigen also can cause problems in patients who do not have them at the time of transplantation. Severely damaging or even destroying the graft, this phenomenon becomes more common the longer the transplant is in place.

Areas of focus

Ongoing research in the Antibody Barriers Project includes:

  • Studies of how antibody development after transplantation affects graft function
  • Laboratory investigations of the cells responsible for producing damaging antibodies
  • Clinical testing of new treatments for lowering or preventing the production of donor-specific antibodies
  • Developing new testing methods and new agents to prevent antibody formation

Outcomes

Researchers at Mayo Clinic's campus in Rochester, Minnesota, have been among the first to develop treatment strategies for reducing antibody levels and achieving successful kidney transplantation from living donors, despite different blood groups or positive crossmatches.

The Transplant Immunology Program team is working to obtain a better understanding of the biology of antibody production, especially as it relates to plasma cells in the spleen and bone marrow, which appear to be the major source of these antibodies. So far, the team has developed novel methods of testing these cells and even new agents that can prevent antibody formation.

The success of these strategies has allowed individuals with kidney failure to avoid lengthy or indefinite waiting periods for deceased donor transplants. The initiative originating from Mayo Clinic's Transplant Immunology Program has developed into the largest such program in the U.S., with over 50 blood-group-incompatible or positive crossmatch transplants carried out to date.

Please contact us for more information about antibody barrier research in the Transplant Immunology Program at Mayo Clinic.