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May 3, 20260 citations

HLA DRB1*01:02 allele is associated with anti-AT1R antibodies production in kidney transplanted patients.

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ICIlaria CarelliARAlessandro RomanoAFAngelo Corso Faini

Key Result

The HLA-DRB1*01:02 allele was significantly associated with higher pre-transplant (p=0.0009) and post-transplant (p<0.0001) anti-AT1R antibody production in kidney transplant recipients.

Key Points

  • This study aims to investigate the influence of selective HLA alleles on the production of anti-AT1R antibodies in kidney transplant recipients.
  • Analyzed a cohort of 59 kidney transplant recipients with HLA haplotype and 52 controls.
  • Tested sera for donor-specific anti-HLA and AT1R antibodies using Luminex and ELISA.
  • Conducted in silico analysis for peptide binding to HLA haplotypes.
  • AT1R-abs were significantly more frequent in patients with the DRB1*01:02 allele, pre-transplant (p = 0.0009) and post-transplant (p < 0.0001).
  • Control group showed rare positivity for AT1R-abs.
  • In silico predictions indicated HLA-DRB1*01:02 binds AT1R peptides with higher affinity.

Study Design

Type

Observational (n=111)

Structured PICO

Does the HLA-DRB1*01:02 allele influence the development of anti-AT1R antibodies in kidney transplant recipients?

P
Population
111 kidney transplant recipients, including 59 carrying the HLA-A*33:01-B*14:02-DRB1*01:02 haplotype and 52 controls.
I
Intervention
Presence of HLA-A*33:01-B*14:02-DRB1*01:02 haplotype (specifically HLA-DRB1*01:02)
C
Comparator
Controls without the specified HLA haplotype
O
Outcome
Development of anti-Angiotensin type 1 receptor antibodies (AT1R-abs) pre- and post-transplantsurrogate

The HLA-DRB1*01:02 allele is associated with a higher likelihood of developing anti-AT1R antibodies in kidney transplant recipients, potentially due to greater peptide binding affinity.

Main Result

p-value: p=<0.0001

Abstract

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.

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Cite This Study

Carelli et al. (2026) conducted an observational in Kidney transplantation (n=111). HLA-A*33:01-B*14:02-DRB1*01:02 haplotype vs. Controls was evaluated on Anti-AT1R antibody development pre- and post-transplant (p=<0.0001). The HLA-DRB1*01:02 allele was significantly associated with higher pre-transplant (p=0.0009) and post-transplant (p<0.0001) anti-AT1R antibody production in kidney transplant recipients.

synapsesocial.com/papers/69f6e5ac8071d4f1bdfc657chttps://doi.org/10.1016/j.humimm.2026.111745
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