Work

#2974 Human leukocyte antigen alleles associated with acute antibody-mediated rejection in kidney transplantation in a Mexican population

Year: 2025

Type: article

Abstract: Background and Aims Acute antibody mediated rejection (AMR) affects 25% of transplant patients. Human leukocyte antigen (HLA) genetic variation is associated with the immune response. The main objective was to determine the association between human leukocyte antigen alleles and susceptibility to acute rejection in kidney transplantation. Method Cross-sectional study. HLA typing was performed in Mexican kidney transplant patients with living or cadaveric donors at least one year after surgery, and the frequencies of allelic and haplotypic blocks were compared between the group with antibody-mediated rejection and the group without rejection. Ancestral, demographic, and clinical information was obtained from patients and medical records. Results 106 patients were included. 61% were male with a median age of 35 years. 59% of the patients had experienced sensitization events prior to transplantation, mainly with blood transfusions, but the median panel reactive antibody (PRA) was 0. 59% of the patients had a standard immunologic risk at the time of transplantation. The aetiology of kidney disease was unknown in 60% of patients, followed by glomerulopathies in 26%. Kidney donors were female (58%) and 30% of transplants were from cadaveric donors. 53% of patients had induction immunosuppression with basiliximab, 87% were on triple-drug maintenance immunosuppression with prednisone, tacrolimus and mycophenolate; median tacrolimus level was 8.7 ng/dl. The highest gene frequencies in the population for class I alleles were A*02 and A*24, B*39 and B*40, C*07 and C*04. Within class II, the highest gene frequencies were DR*04, DR*08, DQA1*03 and DQA1*05, DQB1*03 and DQB1*05, DPA1*01 and DPA1*02, and DPB1*04 and DPB1*02. HLA-C, HLA-DQ and HLA-DP alleles have not been previously reported in the Mexican kidney transplant population. Fifty-seven patients were diagnosed with AMR; at the time of AMR, PRA class I had a median of 3 and class II had a median of 7. 53% of patients with AMR developed donor-specific antibodies. The alleles found to confer susceptibility risk for AMR were B*39 (OR 2.4), C*07 (OR 3.2), DQB1*05 (OR 2.9), and DPB1*04 (OR 3); however, the alleles B*35 (OR 0.29) and C*04 (OR 0.25) were found to be protective. The haplotype block B*39-DR*08 (OR 2.95) was associated with increased risk and the haplotype blocks B*35-C*04 (OR 0.14) and DR*13-DQA1*01-DQB1*06 (0.15) were protective. A subgroup analysis was performed on HLA-C*07 risk alleles, where demographic and clinical variables in patients carrying the C*07 allele were evaluated univariately between the group with AMR and without diagnosis of rejection, in which it was found that male donors donating to patients with C*07 allele are more associated with AMR (P = 0.007), although there was no difference between immunologic risk (P = 0.49) or induction therapy (P = 0.8). For the subgroup with the HLA-DQB1*05 allele, univariate analysis showed that patients in this subgroup had a high immunologic risk at the time of transplantation (P = 0.04), although there was no statistically significant difference in sensitizing events (P = 0.14). Conclusion In the Mexican population, B*39, C*07, DQB1*05 and DPB1*04 alleles confer an increased risk of developing antibody-mediated rejection, so early identification and close monitoring of immunosuppression in these patients is essential to avoid immunological complications of kidney transplantation.

Source: Nephrology Dialysis Transplantation

DOI: 10.1093/ndt/gfaf116.0831