Antibody Barriers Project

One of our major research projects is advancing the science of transplantation to overcome antibody barriers to immediate and long-term transplant success.

One example of these barriers is the action of antibodies against human leukocyte antigens, which are proteins on the surface of cells responsible for regulating the immune system. Cells displaying different varieties of human leukocyte antigen are seen by the body as foreign and an immune response is triggered against them. This reaction can result in organ rejection and is a major cause of both early and late damage to a transplanted organ, also called a graft.

Many transplant candidates develop antibodies against human leukocyte antigen because of past exposure to foreign forms of this antigen, such as through pregnancy, a blood transfusion or a previous kidney transplant that failed. At the time of transplant, 1 in 3 kidney transplant candidates has antibodies that may attack the graft.

Kidney transplantation usually isn't performed if the potential donor has a different blood type than the recipient or if the recipient has preexisting antibodies that recognize donor cells, which is known as a positive crossmatch. In these cases, there's 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 people who don't have these antibodies at the time of transplant. This phenomenon becomes more common the longer the transplanted organ is in place and can severely damage or destroy the graft.

Focus areas

Ongoing research includes:

• Studying how antibody development after transplantation affects graft function.
• Investigating the cells responsible for producing damaging antibodies.
• Clinical testing of new treatments to reduce or prevent 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, were among the first investigators to develop treatment strategies for reducing antibody levels and achieving successful kidney transplantation from living donors despite blood group differences or positive crossmatches.

Today, our research team continues efforts to gain a better understanding of the biology of antibody production, especially as it relates to plasma cells in the spleen and bone marrow, which seem to be the major sources of these antibodies. We've developed novel methods of testing these cells and even new agents that can prevent antibody formation.

The success of these strategies has allowed people with kidney failure to avoid lengthy or indefinite waiting periods for deceased donor transplants. The initiative originating from our Transplant Immunology Program has developed into the largest such program in the United States, with more than 50 transplants performed with incompatible blood groups or positive crossmatches.