Inhibiting a Molecule May Help Transplants Thrive

While much of our collective focus is on enhancing the functions of the immune system, the human immune system can be the human body’s own “worst enemy.” Rheumatoid arthritis, multiple sclerosis, allergies, cytokine storms and celiac disease are all caused by the immune system’s overreaction to foreign bodies. However, one of the most dangerous immune system overreactions is that due to organ transplants.

Scientists work painstakingly to identify the most exact transplant matches in an effort to prevent dangerous and costly transplant rejections. This involves a process known as tissue typing, and the goal is to match the antigens on the tissue of the donor organ as closely as possible to the recipient’s tissue. This can prevent the immune system from sensing that the antigens on the donor organ are foreign and attacking the new organ. Then, doctors prescribe immunosuppressive medications to temper the immune system and further prevent an attack of the replacement organ.

Together, tissue typing and immunosuppressive medications are relatively successful in preventing hyperacute rejection, which can happen immediately after a transplant, and acute organ rejection, which can happen up to three months following the surgery. However, chronic rejection, in which the body slowly attacks the new organ, is much more difficult to treat, because it occurs over years of immune activity. Scientists have been searching for a way to prevent this slow breakdown of chronic rejection.

This was the driving force behind a study by Jordan Pober, the Bayer Professor of Translational Medicine at Yale University, and his team, who have recently identified a molecule of crucial importance in the chronic rejection of transplants. The immune response against transplanted tissue largely takes place in the endothelial cells of the blood vessels, home of the HLA antigens that most often instigate aggressive immune responses in transplant cases. Through a process called membrane attack complex (MAC), the endothelial cells produce molecules that spur T cells to attack. By inhibiting one of those molecules, this aggressive immune response can potentially be prevented.

Preventing chronic rejection without prolonged use of immunosuppressants can potentially save the lives of transplant recipients, as well as minimizing the number of organ transplants that any one patient needs and freeing up those organs for other recipients.

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