ORIGINAL RESEARCH article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1614408
RISK ASSESSMENT OF ANTIBODY-MEDIATED DAMAGE BASED ON THE DETECTION OF HLA AND NON-HLA ANTIBODIES TOWARDS EXTRACELLULAR ANTIGENS BEFORE KIDNEY TRANSPLANTATION
Provisionally accepted
Eulàlia Solà-Porta1*
Dolores Redondo-Pachón1,2Jorge Eguía-Núñez3
Anna Buxeda1,2
José Luís Caro4Javier Gimeno2Luís Campuzano1
Carla Burballa1,2Betty Chamoun2
Sara Sanz-Ureña1Judith Federico-Vega1
Elisenda Alari-Pahissa1Julio Pascual1,5
María José Pérez-Sáez1,2
Marta Crespo1,2*- 1Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
- 2Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
- 3Reference Laboratory of Catalonia, Barcelona, Spain
- 4Hospital Clinic of Barcelona, Barcelona, Spain
- 5Research Institute Hospital 12 de Octubre, Madrid, Spain
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Donor-specific human leukocyte antigens antibodies (HLA-DSA) contribute to antibody-mediated rejection (ABMR) after kidney transplantation (KT). Non-HLA antibodies may play a role in ABMR in the presence of HLA-DSA or the development of microvascular inflammation (MVI) in its absence. Considering both types of antibodies in potential recipients could enhance ABMR/MVI risk assessment. We present a case-control study of 121 KT recipients, 46 with ABMR/MVI diagnosis, and 75 control cases with available sera before and after KT, follow-up HLA antibody monitoring, and biopsies. We determined 60 serum non-HLA antibodies using a multiplex test with an established cutoff. We evaluated their association with ABMR/MVI using a sample median fluorescence intensity (MFI) ratio sum. Following commercial cutoffs, non-HLA antibodies were detected in 87% of patients before KT.We found that a high non-HLA antibody MFI ratio sum before KT and at biopsy were associated with an increased risk of ABMR/MVI, independently of HLA sensitization or HLA-DSA (OR=1.039, p=0.014 and OR=1.036, p=0.024). Antibodies against extracellular non-HLA antigens were associated with ABMR/MVI before KT (OR=1.053, p=0.040), but at diagnosis, only antibodies against intracellular non-HLA were (OR=1.062, p=0.018). These findings suggest that non-HLA antibody assessment offers valuable complementary information, regardless of HLA sensitization, though appropriate cut-offs should be explored.
Keywords: Non-HLA antibodies, HLA, ABMR, Antibody-mediated Rejection, MVI, microvascular inflammation, GSTT1
Received: 18 Apr 2025; Accepted: 16 Jul 2025.
Copyright: © 2025 Solà-Porta, Redondo-Pachón, Eguía-Núñez, Buxeda, Caro, Gimeno, Campuzano, Burballa, Chamoun, Sanz-Ureña, Federico-Vega, Alari-Pahissa, Pascual, Pérez-Sáez and Crespo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Eulàlia Solà-Porta, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Marta Crespo, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.