Session Name: Kidney Chronic Antibody Mediated Rejection
Session Date & Time: None. Available on demand.
*Purpose: Correlation between antibody-mediated rejection (ABMR) and HLA donor-specific antibodies (DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of other detrimental antibodies contributing to ABMR. The role of non-HLA antibodies on outcomes is not well known.
*Methods: We retrospectively assessed KT biopsies scored according to Banff’15 classification. Pre- and post-KT serum samples were checked for HLA and non-HLA antibodies (MICA-Ab, angiotensin II type 1 receptor (AT1R)-Ab, endothelin-1 type A receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)). We also analyzed HLA epitope mismatches between donors and recipients.
*Results: One-hundred eighteen patients with normal (n=19), ABMR histology (n=52) or IFTA (n=47) in their biopsy were studied. Graft survival was worse in ABMR patients (p=0.003). Pre-KT HLA-DSA were more frequent in ABMR cases (p=0.006). At biopsy, 73% ABMR patients had HLA-DSA (p<0.001). Pre-KT AT1R-Ab were more frequent in ABMR compared with IFTA and normal cases (p=0.003), without differences in other non-HLA antibodies. Both total class II and DRB1 epitope mismatches were associated with ABMR-DSA+. Fourteen patients with histological ABMR (27%) had no detectable HLA-DSA post-KT and only 3 had non-HLA Ab. However, they showed similar biopsy changes and graft survival compared with ABMR-DSA+. Pre- or post-KT non-HLA antibodies other than AT1R-Ab were detected only in a small subset of ABMR ($graphic_). Multivariate analysis showed that both pre-KT HLA-DSA and AT1R-Ab (DSA: OR: 3.39 [1.20-9.59], p=0.021; AT1R-Ab: OR: 5.31 [1.75-16.10], p=0.003) were strong independent predictors of ABMR-DSA+.
*Conclusions: Despite highly prevalent HLA-DSA before and after transplantation in KT with histological ABMR, 27% of cases did not show circulating HLA-DSA. Pre-KT AT1R-Ab associated with ABMR-DSA+, but not MICA-Ab, ETAR-Ab or EC-XM+. Epitope mismatch predicted both de novo appearance of DRB-DSA and ABMR-DSA+. Detection of pre-KT HLA-DSA and/or AT1R-Ab, together with HLA epitope mismatch assessment, are valuable tools for better DSA and ABMR prediction in KT patients.
To cite this abstract in AMA style:Crespo M, Llinás L, Redondo D, Butler C, Gimeno J, Pérez-Sáez M, Buxeda A, Arias C, Folgueiras M, Sanz S, Valenzuela N, Reed EE, Pascual J. Non-HLA Antibodies and Eplet Mismatches in Cases with Histological Picture of Antibody-Mediated Rejection with and without HLA Donor-Specific Antibodies [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/non-hla-antibodies-and-eplet-mismatches-in-cases-with-histological-picture-of-antibody-mediated-rejection-with-and-without-hla-donor-specific-antibodies/. Accessed September 24, 2021.
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