The Impact of Epitope Mismatch Load and Shared Targeting Epitopes between De Novo Donor Specific Antibody (DSA) and Non-DSA Third Party HLA Antibody on Lung Transplantation Outcomes

A. Zhang¹, D. Good¹, D. Thomas¹, J. Allen¹, K. McCurry², M. Budev²

¹Allogen Laboratories, Cleveland Clinic, Cleveland, OH, ²Cleveland Clinic, Cleveland, OH

Meeting: 2020 American Transplant Congress

Abstract number: 87

Keywords: Epitopes, Graft function, HLA antibodies, Lung transplantation

Session Information

Session Name: From Bench to Community to Bedside in Lung Transplantation

Session Type: Oral Abstract Session

Date: Saturday, May 30, 2020

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

Presentation Time: 4:15pm-4:27pm

Location: Virtual

*Purpose: Rapid advancements in HLA typing and antibody identification technologies allow for enhanced HLA compatibility assessment at the epitope level to aid in the reduction of organ transplantation immunologic risk. This study investigated the effects of pre Lung Transplantation (LuT) HLA-Epitope Mismatch Load (EpiMmL) and post LuT shared epitope targets amid De Novo Donor Specific Antibody (dDSA) and Non-DSA (dN-DSA) HLA antibody on LuT outcomes.

*Methods: Epitope analysis was retrospectively performed using HLA-Matchmaker version 2 on patient/donor (P/D) pairs who had high resolution typing and underwent LuT during 2012-2019. The association of pre-LuT EpiMmLs to the development of dDSA was analyzed among 168 P/D pairs. At post-LuT phase, 192 non-sensitized patients who developed dDSA without and with dN-DSA (Gp1 and Gp2) were compared for total antibody mediated rejection (AMR), clinical AMR (with graft dysfunction), bronchiolitis obliterans syndrome (BOS), and chronic lung allograft dysfunction (CLAD). The antigen specificity expansion frequencies among HLA-A, B, DR, and DQ loci was analyzed among 72 subjects in Gp2.

*Results: EpiMmLs of Class I, Class II, and single loci of HLA-A, B, C, DR, and DQ were all significantly higher in P/D’s with dDSAs than those without dDSAs ( p<0.001 and p<0.05, Table 1a). 129 out of 192 recipients (67%) developed dDSA, 32 (25%) in Gp1 and 97 (75%) in Gp2. There were no statistical differences in BOS, CLAD, and total AMR between Gp1 and Gp2. However, Gp2 patients exhibited significantly more clinical AMR than Gp1 patients (p<0.001, Table 1b). Development of dN-DSAs sharing public epitopes with dDSAs was observed in 72/97 (74%) patients in Gp2. The epitope specificity expansion of dN-DSA was most noticeable in patients with DQ antibodies, where 53/72 (74%) showed dDSAs with dN-DSAs as compared to individuals with HLA-A, B, or DR antigen expansions (p<0.001, Table 1c).

*Conclusions: EpiMmL is a good Pre-LuT predictor of dDSA development. Interestingly, the increased incidence of post-LuT clinical AMR in patients with dDSA + dN-DSA compared to dDSA alone highlights the possibility that, in combination, such dN-DSA HLA antibodies are synergistic to dDSA in augmenting graft damage. The pathogenic mechanisms could be due to functional differences or merely quantitative. Thus, in addition to dDSA, epitope sharing dN-DSAs, especially HLA-DQ, can increase the risk of graft dysfunction.

To cite this abstract in AMA style:

Zhang A, Good D, Thomas D, Allen J, McCurry K, Budev M. The Impact of Epitope Mismatch Load and Shared Targeting Epitopes between De Novo Donor Specific Antibody (DSA) and Non-DSA Third Party HLA Antibody on Lung Transplantation Outcomes [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/the-impact-of-epitope-mismatch-load-and-shared-targeting-epitopes-between-de-novo-donor-specific-antibody-dsa-and-non-dsa-third-party-hla-antibody-on-lung-transplantation-outcomes/. Accessed May 29, 2025.

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