Researchers reduce donor heart rejection with desensitizing antibodies

On the 50th anniversary of using heart transplantation to save lives, researchers from the Pitié-Salpêtrière Hospital in Paris revealed a technique that could reduce the risk of patients rejecting donor hearts.

The method, presented May 1 at Heart Failure 2017, an annual conference hosted by the European Society of Cardiology in Paris, includes desensitizing patient antibodies that can control a patient's likelihood of rejecting a donor heart.

"Most centers do not perform heart transplantation in patients with a high donor-specific anti-human leukocyte antigen (HLA) antibody (DSA) levels since the risk of antibody-mediated rejection is high, particularly hyper-acute rejection," said Guillaume Coutance, MD, the lead author on the study and a cardiologist at Pitié-Salpêtrière, in a statement. "Patients then have to wait for a donor with different anti-HLA antigens."

In 2009, Pitié-Salpêtrière began a desensitization program to test how effective it was in reducing the chance of heart transplantation rejection in patients from 2009 to 2015. There were more than 500 patients who, on average, were 50 years old. About 77 percent were men.

To determine what type of desensitization patients received depended on their DSA levels, which the researchers measured by mean fluorescence intensity (MFI). MFIs between 500 and 1,000 were considered low and an MFI above 1,000 was considered high. All the patients in the study received anti-thymocyte globulins and conventional immunosuppressive therapy, the study said.

About 46 percent of patients had no DSA, 17 percent had low levels and 37 percent had high levels.

Additionally, patients with low DSA levels received intravenous immunoglobulins while patients with higher levels were treated with plasmapheresis before and after transplantation.

Patients were then followed for an average of 3.7 years, and researchers compared survival rates in each of the three groups.

Results showed that length of survival after transplantation was similar between all the groups, even after the researchers adjusted for age, sex and other factors. At one year and at the end of follow-up, survival for patients with no DSA was 79 percent and 73 percent, 80 percent and 72 percent in patients with low DSA and 84 percent and 76 percent in patients with high DSA levels, respectively.

"By desensitizing patient's antibodies, those with high immunological risk experience similar survival to patients without DSA,” Coutance said. “Pre- and post-operative plasmapheresis results in a dramatic drop in DSA levels, which reduces the risk of hyper-acute rejections and early antibody-mediated rejections. Intravenous immunoglobulins will neutralize DSA for weeks. This desensitization program could shorten waiting times and increase access to transplantation for patients at high immunological risk. However, it will probably not increase the number of transplantations since donor shortage is the limiting factor."