Non-HLA Antibodies and Eplet Mismatches in Cases with Histological Picture of Antibody-Mediated Rejection with and without HLA Donor-Specific Antibodies

M. Crespo¹, L. Llinás², D. Redondo², C. Butler³, J. Gimeno⁴, M. Pérez-Sáez², A. Buxeda², C. Arias², M. Folgueiras², S. Sanz², N. Valenzuela³, E. E. Reed³, J. Pascual²

¹Nephrology and Kidney Transplantation, Hospital del Mar, Barcelona, Spain, ²Nephrology, Hospital del Mar, Barcelona, Spain, ³UCLA Immunogenetics Center, UCLA, Los Angeles, CA, ⁴Pathology, Hospital del Mar, Barcelona, Spain

Meeting: 2021 American Transplant Congress

Abstract number: 1044

Keywords: Antibodies, Epitopes, HLA antibodies, Rejection

Topic: Clinical Science » Kidney » Kidney Chronic Antibody Mediated Rejection

Session Information

Session Name: Kidney Chronic Antibody Mediated Rejection

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*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 May 29, 2025.

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