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 regulation of the immune system. Cells displaying different varieties of human leukocyte antigen are seen as foreign and thus trigger an immune response against them. This reaction can result in organ rejection and is a major cause of both early and late graft damage.

Many transplant candidates develop antibodies against human leukocyte antigen because of past exposure to foreign forms of this antigen, through pregnancy, a blood transfusion or a previous (failed) kidney transplant, for example. 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 usually isn't performed if the potential donor has a different blood type than the recipient or if the recipient is shown to have preexisting antibodies that recognize donor cells (known as a positive crossmatch). In these circumstances, there's a high risk that the transplanted kidney would be quickly destroyed as a result of antibody binding.

Antibodies against human leukocyte antigen can also cause problems in patients who don't have them at the time of transplantation. This phenomenon becomes more common the longer the transplant is in place and can severely damage or destroy the graft.

Focus areas

Ongoing research in this project on antibody barriers includes:

• Studying how antibody development after transplantation affects graft function
• Investigating the cells responsible for producing damaging antibodies
• Clinical testing of new treatments for reducing or preventing 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 different blood groups or positive crossmatches.

Today, our research team continues efforts 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. 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 patients 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 U.S., with more than 50 transplants performed with incompatible blood groups or positive crossmatches.