Antibodies Provide Clues to Transplant Rejection Risk

Transplant recipients who receive a kidney, heart, or lung often develop an immune response to the foreign tissue in the form of antibodies referred as donor-specific Human Leukocyte Antigen (HLA) antibodies. Some patients may already have these antibodies before their transplant because they have been exposed to blood products or previous transplants.

An international collaborating team of scientists led by those at Saint-Louis Hospital (Paris, France) designed a study to determine the greatest risk for losing a transplanted organ based on the characteristics and function of donor-specific HLA antibodies. Their study included 125 kidney transplant patients with donor-specific anti-HLA antibodies detected in the first year post-transplant. Renal tissue from the biopsies was fixed in acetic-formol-absolute alcohol fixative and stained with Masson’s trichrome and periodic acid–Schiff. All of the graft biopsies were scored and graded from 0 to 3.

All kidney transplant recipients were tested for circulating donor specific anti-HLA-A, -B, -Cw, -DR, -DQ, and –DP antibodies in serum samples obtained one year after transplantation or during an episode of acute rejection within one year after transplantation. Single-antigen flow bead assays (One Lambda, Inc.; Canoga Park, CA, USA) were used on a Luminex platform. HLA typing of the recipients was performed by INNO-LiPA HLA typing kit (Innogenetics; Gent, Belgium). For all kidney transplant donors, tissue typing was initially performed using the microlymphocytotoxicity technique with tissue typing trays at transplantation and was confirmed by molecular biology.

The investigators found that the presence of certain donor-specific HLA antibodies, namely immunoglobulin G3 (IgG3) and IgG4 subclasses correlated with distinct patterns of antibody-mediated injury to the transplanted organ. Patients with mostly IgG3 donor-specific HLA antibodies had a higher likelihood of organ rejection soon after transplantation. If rejection occurred in those with mostly IgG4 antibodies, it was usually much later after transplantation.

Carmen Lefaucheur, MD, PhD, the lead author of the study, said, “Our clinical investigation may help in the future to identify the patients that will require interventions to prevent the loss of a transplanted organ. 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.” The study was published on August 20, 2015, in the Journal of the American Society of Nephrology.

Related Links:
Saint-Louis Hospital
One Lambda Inc. 
Innogenetics