During solid organ transplant, there is a risk of the donor organ being rejected via antibodies made by the recipient. The most well studied antigens against which antibodies form are the polymorphic Human leukocyte antigens (HLA). Often patients will be checked for HLA mismatches and donor specific HLA antibodies that may cause rejection before being receiving a transplant. However, even patients who have been HLA matched can go through antibody-mediated rejection (AMR). This highlights the importance of looking for other antibodies that are responsible for these rejections. At UCLA, if a transplant patient presents with AMR, and is not positive for any donor specific HLA antibodies we will search for other known antibodies that may cause AMR. Currently the four other non-HLA antibodies we check for are MHC (major histocompatibility complex) class I-related chain A (MICA), angiotensin II type 1 receptor (AT1R) and anti-endothelial cell antibodies. However, even patients who are negative for antibodies against these can go through acute antibody-mediated rejection based on biopsy results. The goal of this study was to identify any patterns in the AMR episodes patients experienced and whether patients who may not have any identifiable antibodies can still benefit from antibody mediated treatment.
We retrospectively reviewed 12 patients who received a renal allograft at UCLA Health who suffered one or more episodes of acute or chronic antibody-mediated rejection. In 3 patients, rejection led to complete allograft deterioration and required hemodialysis and replacement on the transplant list. The other 9 patients seemed to have recovered from their rejection episode. All but one of the patients were considered to be low immunological risk recipients pre-transplant. We did a chart review on these patients and looked at their antibody levels, as well as biopsy results and the treatment they received for their episodes of rejection. These patients were observed retrospectively and there was no control group to compare them to. The age of the patients varied from 22 to 64 years old at age of transplant. The treatments they received were standard for antibody mediated rejection of an organ. Treatments included: Plasmapheresis, IVIG and Thymoglobulin.
25% of patients had complete graft failure(patients 5,6 and 9), 75% recovered back to their baseline creatinine levels. Patient 5 tested positive for antibodies against AT1R, patient 6 did not test positive for any non-HLA antibodies and patient 9 tested positive for MICA.Of the 12 transplants, 4 were from a Deceased donor, 5 were living unrelated donors, and 3 were related, either parent orsibling. Of the 3 patients whose condition did not improve, 2 received their transplant due to glomerulonephritis and NSAID/methotrexate damage while the other patients’ reason for transplant was unknown due to the procedure being performed in another country. However, this patient was the only one of the patients whose graft failed that tested positive for MICA. One patient had received 2 prior renal transplants, however, they managed to recover from the AMR via standard treatment methods. There were also 2 patients who did not test positive for any antibodies during their AMR. Figure 1 demonstrates the number of patients that presented certain antibodies during the AMR episodes. The patients were treated with the standard treatment for antibody mediated rejection i.e. IVIG, Plasmapheresis, ATG. The majority of patients recovered well when they were broadly treated for antibodies even though if they did not test positive for any antibody that we currently can test for. There were no patterns that could be found amongst the patients, including their age, sex, cause of ESRD, relationship to donor and their immunosuppressant medications.
Given that 9 out of the 12 patients recovered to baseline, the antibody targeted therapies worked well. Even patients for whom serological testing revealed no HLA, AT1R, endothelial cell or MICA antibodies responded to standard AMR therapy, suggesting that there are other antibodies involved in antibody-mediated rejection. When treating a case of antibody mediated rejection, physicians should keep in mind that if a patient does not present positive for any antibodies we currently search for, they may still benefit from receiving antibody-targeted treatment. Furthermore, future studies can look to expand the number of patients enrolled, as well as request for the treating team to check for antibodies beyond the ones that are currently searched for.