Hla-dq Epitope Mismatch Predicts De Novo Donor-Specific Antibody Formation and Acute Cellular Rejection After Living Donor Liver Transplantation

K. Ono, K. Ide, Y. Tanaka, M. Ohira, H. Tahara, N. Tanimine, S. Akimoto, Y. Imaoka, K. Sato, H. Yamane, N. Tsukiyama, R. Ide, T. Mochizuki, H. Ohdan

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health S, Hiroshima University, Hiroshima City, Japan

Meeting: 2021 American Transplant Congress

Abstract number: 654

Keywords: Epitopes, Immunogenicity, Liver transplantation, T cell reactivity

Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes

Session Information

Session Name: Biomarkers, Immune Assessment and Clinical Outcomes

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: Epitope mismatch (MM) effect on living donor liver transplantation (LDLT) has not been studied in detail. This study aimed to investigate the role of epitope MM in predicting de novo donor-specific antibody (dn-DSA) formation and the relationship between epitope MM and T cell immune response in LDLT.

*Methods: Forty-five recipients (39 ABO-blood-type compatible, 6 ABO incompatible) were enrolled. Epitope MM levels for HLA class I (A, B, C) and class II (DRB1, DQB1) were determined by HLAMatchmaker. For all recipients, anti-HLA antibodies were analyzed before and annually after transplantation. Mean fluorescence intensity (MFI) above 1,000 for DSAs against HLA-A, -B, -C, -DRB1, and -DQB1 was considered positive. Recipient T-cell responses to allostimulation were evaluated by MLR assay before LDLT. CD4⁺ and CD8⁺ T-cell stimulation index (SI) and CD25 expression in proliferating CD8⁺ T-cells were quantified using multiparameter FCM analysis.

*Results: Nine patients (20%) developed dn-DSAs; almost all dn-DSAs were against HLA class II antigens. Total HLA allele MM and HLA-A, -B, -C, -DRB1 and -DQB1 allele MM were not associated with dn-DSAs. Patients with dn-DSAs had a significantly higher number of HLA-DQ epitope MMs (7.8 ± 3.0 vs. 4.6 ± 5.4, P<0.05). The probability of dn-HLA-DQB1 DSA formation was higher for the patients with >9 HLA-DQ epitope MMs. A receiver operating characteristic (ROC) analysis showed that the number of HLA-DQB1 epitope MMs was strongly predictive of dn-HLA-DQ DSA (area under the curve [AUC], 0.771; P <0.01). Patients with ACR in the first month had a higher number of HLA-DQ epitope MMs (8.7 ± 6.7 vs. 4.6 ± 4.6; P<0.05). The probability of ACR was higher for HLA-DQB1 epitope MMs >7. ROC analysis for ACR showed strong predictive values of HLA-DQB1 epitope MMs (AUC, 0.728; P<0.05). There was no significant difference in the SI for the CD4⁺ and CD8⁺ T-cell responses in patients with low-(<7) and high-load (≥7) of HLA-DQB1 epitope MM. However, the CD25 expression in proliferating CD8⁺ T-cells was higher in the high-load patients.

*Conclusions: HLA-DQB1 epitope MM is associated with dn-DSA formation and ACR after LDLT. Further studies are required to evaluate the clinical utility of epitope matching.

To cite this abstract in AMA style:

Ono K, Ide K, Tanaka Y, Ohira M, Tahara H, Tanimine N, Akimoto S, Imaoka Y, Sato K, Yamane H, Tsukiyama N, Ide R, Mochizuki T, Ohdan H. Hla-dq Epitope Mismatch Predicts De Novo Donor-Specific Antibody Formation and Acute Cellular Rejection After Living Donor Liver Transplantation [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/hla-dq-epitope-mismatch-predicts-de-novo-donor-specific-antibody-formation-and-acute-cellular-rejection-after-living-donor-liver-transplantation/. Accessed May 11, 2025.

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