Molecular Features of HLA Mismatches as Predictors of De Novo DSA Development: A Single Center Experience

V. Jucaud¹, L. Rebellato², K. Briley², C. Haisch², S. Kendrick³, H. Jones³, K. Mclawhorn³, D. Leeser², M. Everly¹

¹Terasaki Research Institute, Los Angeles, CA, ²East Carolina University, Greenville, NC, ³Eastern Nephrology Associates, Greenville, NC

Meeting: 2020 American Transplant Congress

Abstract number: 103

Keywords: Epitopes, HLA antibodies, Immunogenicity, Kidney transplantation

Session Information

Session Name: Histocompatibility and Immunogenetics

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:45pm

Presentation Time: 3:15pm-3:27pm

Location: Virtual

*Purpose: Several molecular features (MoFs) of HLA mismatches (MMs) are currently used to predict the development of de novo donor-specific anti-HLA antibodies (dnDSA). The purpose of this study is to evaluate the independent and concomitant impact of several MoFs of HLA MMs on the development of dnDSA against several HLA loci.

*Methods: We retrospectively studied 236 HLA-mismatched kidney recipients transplanted between 2011 and 2016. All recipients received calcineurin inhibitors, did not have preformed DSA, were HLA-typed by NGS for HLA-A, -B, -C, -DRB1, -DRB345, -DQB1, -DPB1, and were screened for dnDSA using Single Antigen Beads with a median follow-up of 2.26 years. We used E3, an HLA immunogenicity software, to generate the following MoFs of HLA MMs: amino acid mismatch load (AML); electrostatic charge difference (ECD); hydrophobic difference (HD); mismatched HLA antibody epitope load (AbEpiL); and PIRCHE-II.

*Results: Among the 236 recipients, we observed a total of 2123 HLA MMs, of which 253 induced a dnDSA. The 3 year cumulative event rate of dnDSA development against the different HLA loci was statistically different (p<0.001). For HLA-A, -C and -DRB1 MMs, none of the MoFs were significantly associated with the development of dnDSA. From a univariate perspective and for HLA-B MMs, all MoFs except HD were significantly associated with the development of dnDSA, yet only PIRCHE-II was statistically significant in a multivariate analysis. Similarly, for HLA-DRB345 MMs, the AML, HD and PIRCHE-II were significantly associated with the development of dnDSA, but only the ECD was statistically significant in a multivariate analysis. Moreover, for HLA-DQB1 MMs, all MoFs were significantly associated with the development of dnDSA, yet only ECD was statistically significant in a multivariate analysis. Last, for HLA-DPB1 MMs, the ECD and HD were significantly associated with the development of dnDSA, but not in the multivariate analysis (Table 1).

*Conclusions: None of the MoFs of HLA MMs were strong predictors of dnDSA development, although some are associated with the development of dnDSA in both univariate and multivariate analyses. Therefore, HLA immunogenicity-based dnDSA development risk-stratification remains to be fully elucidated before its clinical application.

To cite this abstract in AMA style:

Jucaud V, Rebellato L, Briley K, Haisch C, Kendrick S, Jones H, Mclawhorn K, Leeser D, Everly M. Molecular Features of HLA Mismatches as Predictors of De Novo DSA Development: A Single Center Experience [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/molecular-features-of-hla-mismatches-as-predictors-of-de-novo-dsa-development-a-single-center-experience/. Accessed May 9, 2025.

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