Researchers Identify Two Antibodies Responsible for Organ Rejection in Transplant Patients

Findings may better predict organ rejection before transplantation.

Physicians could soon be able to determine if a transplanted organ may be rejected prior to surgery, thanks to a new study published in the Journal of the American Society of Nephrology. The findings of the study may help doctors identify patients who need aggressive treatments to safeguard the health of their new organ.

Those who receive a transplanted organ, such as a kidney, heart or lung, often can develop an immune response to the foreign tissue in the form of antibodies called donor-specific HLA antibodies. Some patients may already have these antibodies prior to surgery because they have been exposed to blood products or previous transplants. While the presence of HLA antibodies is typically not a good sign, it does not always result in a poor outcome for patients.

Through a collaboration of 2 transplant centers in France and the United States, Carmen Lefaucher, MD, PhD (Saint-Louis Hospital, in Paris) and his colleagues designed a study to determine the greatest risk for losing a transplanted organ based on the characteristics and function of donor-specific HLA antibodies. The study evaluated 125 kidney transplant patients with donor-specific anti-HLA antibodies detected in the first year post-transplant.

The researchers found that the presence of 2 subclasses of donor-specific HLA antibodies, lgG3 and lgG4, were associated with distinct patterns of antibody-mediated injury to the transplanted organ. Patients with a higher count of lgG3 donor-specific HLA antibodies were more likely to experience organ rejection soon after transplantation. Rejection occurred much later in patients with higher counts of lgG4 antibodies.

“Our clinical investigation may help in the future to identify the patients that will require interventions to prevent the loss of a transplanted organ,” Dr. Lefaucher said. “Also, based on what we learned in this investigation, more studies will be initiated to further elucidate why some patients seem to maintain good outcomes while others demonstrate accelerated deterioration of the transplanted kidney in the presence of circulating donor-specific HLA antibodies.”

Stanley Jordan, MD, of Cedars-Sinai Medical Center, noted that if the findings are supported by additional studies, it could be of great help in counseling patients and possibly avoiding costly immunotherapy to reduce what appears to be largely benign donor-specific HLA antibodies.

“Lefaucher et al. are to be commended for this important work, which further enlightens our understanding of the natural history of immunodominant donor-specific HLA antibodies and their effect on allograft pathology and outcomes,” he wrote.