Impact of low-level pretransplant donor-specific antibodies detected by the Luminex platform on acute rejection and long-term graft survival.

Background: The Luminex platform, where beads are coated with single human leukocyte antigens (HLA), detects HLA antibodies with higher sensitivity and specificity compared to complement-dependent cytotoxicity (CDC) assay and flow cross-match (FCXM). The clinical significance of donor-specific antibodies (DSAs) detected by this method is still under investigation.

Aim: To report the impact of low-level pretransplant DSAs detected by the Luminex platform on the rates of acute rejection (AR), allograft function, and long-term graft survival.

Methods: This retrospective study was conducted at the Immunology Department of Sindh Institute of Urology and Transplantation, Karachi, Pakistan between January 2013 and December 2022. During this period 2714 patients were transplanted. Out of these patients 78 (2.9%) patients had low-level DSAs detected by the Luminex flow beads method and were negative by CDC and FCXM with their donors. All recipients received ABO-compatible live-related kidney transplants. All patients had a minimum follow-up of 1 year. Graft rejection rates, graft function, and patient and graft survival were analyzed. The estimated glomerular filtration rate was calculated by the full CKD-EPI formula.

Results: The mean age of all recipients was 29.57 ± 10.11 years and 34.53 ± 9.09 years for the donors. In 48 (61.5%) patients, the cause of end-stage kidney disease was unknown. DSA against HLA class I was detected in 36 (46.1%) patients, class II in 35 (44.8%) patients, and both class I and II in 7 (8.9%) patients. AR episodes were encountered in 8 (10.3%) cases. Seven (87.5%) had T cell mediated rejection (type IA) and one acute antibody-mediated rejection. Antibody status was re-evaluated at the time of biopsy-proven ARs. Five (62.5%) patients lost their DSAs, while three (37.5%) had persistent DSAs. The mean estimated glomerular filtration rate at 1 year was 80.56 ± 27.48 mL/min/1.73 m² and at the last follow-up 73.41 ± 28.80 mL/min/1.73 m². The 1-year and 10-year patient and graft survival rates were 99% and 79% and 95% and 75%, respectively. During the follow-up period, 10 (12.8%) patients died, 8 patients had a functioning graft, and 2 patients had failed grafts. Eight patients died due to cardiopulmonary arrest, and two died due to sepsis with failed grafts.

Conclusion: Patients with pretransplant low-level DSAs on Luminex without CDC and FCXM reactivity had good allograft outcomes at 1 year and 10 years as long as they are induced with biological agents and given potent maintenance immunosuppressants.