HLA, Non-HLA Antibodies, and Eplet Mismatches in Pediatric Liver Transplantation: Observations From a Small, Single-Center Cohort

• Published in: Experimental and clinical transplantation Vol. 17; no. Suppl 1; pp. 6 - 17
• Main Authors: Ekong, Udeme D, Antala, Swati, Bow, Laurine, Sese, Doreen, Morotti, Raffaella, Rodriguez-Davalos, Manuel, Gan, Geliang, Deng, Yanhong, Emre, Sukru H
• Format: Journal Article
• Language: English
• Published: Turkey 01-01-2019
• Subjects: Adolescent; Age Factors; Child; Child, Preschool; Connecticut; Female; Graft Rejection - immunology; Graft Rejection - prevention & control; Graft Survival - drug effects; Histocompatibility; Histocompatibility Testing; HLA Antigens - immunology; Humans; Immunosuppressive Agents - therapeutic use; Infant; Isoantibodies - immunology; Liver Transplantation - adverse effects; Male; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Young Adult; Connecticut
• ISSN: 1304-0855; 2146-8427
• DOI: 10.6002/ECT.MESOT2018.L30

To identify the risk of developing acute rejection, allograft fibrosis, and antibody-mediated rejection, a retrospective review of pediatric patients who underwent liver transplant between July 31, 1998 and February 29, 2016 and had donor-specific antibodies measured at time of liver biopsy was undertaken.
HLAMatchmaker Software (http://www.hlamatchmaker.net) was used to define epitope mismatches between donors and recipients and to predict de novo donor-specific antibody risk. Epitope mismatches were evaluated for their immunogenicity.
In our group of 42 recipients, 20 (48%) had donor-specific antibodies. Having an antibody against HLA-DQB1*02 was associated with acute rejection (66.6% vs 36%; P = .024). We found that DQ epitope mismatch load was greater in recipients with class II donor-specific antibodies (9.7 vs 3.6; P = .001). HLA-DQ (7.4 vs 3.6; P = .04) and HLA-DR (8.8 vs 3.8; P = .04) epitope mismatch loads were higher in recipients with DQ + DR donor-specific antibodies. A high portal fibrosis score was associated with higher mismatch load at the DQ locus (P = .005) and DQ + DR loci (P = .03). Having > 5 or > 6 epitope mismatch loads at the DQ locus identified a threshold above which development of DQ donor-specific antibodies would occur (area under the curve = 0.878). Mismatches for eplet 4Q, 45GE, 52PQ, and 52PL, thought to be immunodominant epitopes, were observed for several recipients.
Knowledge of epitope mismatches between recipients and donors may aid transplant physicians in devising immunosuppression strategies.