Human immunology · 2026
HLA DRB1*01:02 allele is associated with anti-AT1R antibodies production in kidney transplanted patients.
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Carelli Ilaria, Romano Alessandro, Faini Angelo Corso, Caorsi Cristiana, Togliatto Gabriele Maria, Rosso Claudia Maria, Mazzola Gina, Garino Elena, Alizzi Silvia, Magistroni Paola, Biancone Luigi, Cantaluppi Vincenzo, Vaisitti Tiziana, Deaglio Silvia, Amoroso Antonio
Аннотация
BACKGROUND: Kidney transplantation is lifesaving treatment for end-stage renal disease, yet immune-mediated complications limit long-term graft survival. Non-HLA antibodies (NHLA), particularly anti-Angiotensin type 1 receptor antibodies (AT1R-abs), are emerging mediators of graft injury. This study investigated whether selective HLA alleles influence AT1R-ab development in kidney transplant recipients.
MATERIAL AND METHODS: We analyzed a cohort of 59 kidney recipients carrying the HLA-A*33:01-B*14:02-DRB1*01:02 haplotype and 52 controls. Pre- and post-transplant sera were tested for donor-specific anti-HLA antibodies via Luminex-based single antigen bead assay and AT1R-ab via enzyme-linked immunosorbent assay and categorized as positive (≥17 U/mL), intermediate (10.1-16.9 U/mL) and negative (≤10 U/mL). In silico analysis were performed to assess peptide binding to HLA haplotypes.
RESULTS: AT1R-abs were markedly enriched in the DR1 patients, both pre- (p = 0.0009) and post-transplant (p < 0.0001), at variance with controls, who were rarely positive. In silico prediction revealed that HLA-DRB1*01:02, typically the involved DRB1*01 subtype of the above-mentioned haplotype, can present AT1R peptides with greater binding affinity.
CONCLUSIONS: These results suggest a possible genetic link between HLA haplotypes and AT1R-ab development in kidney transplant recipients, probably due to a higher binding affinity of some AT1R-derived peptides to HLA-DRB1*01:02. Understanding this association may enable personalized immunosuppressive therapies.
MATERIAL AND METHODS: We analyzed a cohort of 59 kidney recipients carrying the HLA-A*33:01-B*14:02-DRB1*01:02 haplotype and 52 controls. Pre- and post-transplant sera were tested for donor-specific anti-HLA antibodies via Luminex-based single antigen bead assay and AT1R-ab via enzyme-linked immunosorbent assay and categorized as positive (≥17 U/mL), intermediate (10.1-16.9 U/mL) and negative (≤10 U/mL). In silico analysis were performed to assess peptide binding to HLA haplotypes.
RESULTS: AT1R-abs were markedly enriched in the DR1 patients, both pre- (p = 0.0009) and post-transplant (p < 0.0001), at variance with controls, who were rarely positive. In silico prediction revealed that HLA-DRB1*01:02, typically the involved DRB1*01 subtype of the above-mentioned haplotype, can present AT1R peptides with greater binding affinity.
CONCLUSIONS: These results suggest a possible genetic link between HLA haplotypes and AT1R-ab development in kidney transplant recipients, probably due to a higher binding affinity of some AT1R-derived peptides to HLA-DRB1*01:02. Understanding this association may enable personalized immunosuppressive therapies.