SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1633853
This article is part of the Research TopicAntibody-Mediated Rejection After Solid Organ TransplantationView all 14 articles
Association of Donor-Specific Antibodies with Adverse Outcomes in Solid Organ Transplantation: A Systematic Review and Meta-Analysis of 69 Studies
Provisionally accepted
- Tianjin First Central Hospital, Tianjin, China
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Abstract Importance Preformed donor-specific antibodies (pre-DSAs) are a significant immunologic barrier in solid organ transplantation (SOT), yet their association with post-transplant outcomes lacks consensus, limiting standardized clinical management. Objective To determine the association between pre-DSA and posttransplant complications, including antibody-mediated rejection (AMR), T cell-mediated rejection (TCMR), graft loss, and patient mortality, with subgroup analyses stratified by organ type and MFI thresholds (1,000 cutoff). Data Sources Systematic review of 3,322 studies from PubMed, Embase and the Cochrane Library (from inception to February 2024) following the PRISMA guidelines. Study Selection Sixty-nine observational studies (22,737 transplant recipients; 3,787 pre-DSAs+), including retrospective and prospective cohorts, encompassing kidney (KT) (41 studies), liver (LT) (13), lung (6), heart (3), and other organ transplants. Main Outcomes and Measures Primary: AMR, TCMR, graft loss, patient death. Secondary: Biliary complications, bacteremia, delayed graft function (DGF). Results Pre-DSAs positivity conferred significantly elevated risks of AMR (RR=5.21, 95%CI 4.01–6.79), graft loss (RR=2.11, 1.72–2.60), and mortality (RR=1.62, 1.39–1.89) compared with pre-DSAs–negative recipients, with marked heterogeneity across organ types. KTs faced the highest risk of AMR risk (RR=6.09, 4.39–8.46), whereas LT recipients exhibited elevated mortality (RR=1.81, 1.30–2.53) but lower AMR rates (RR=1.81 vs. KT). The thoracic organs (heart/lung) had no significant association with AMR (RR1.32, 0.86–2.03). Stratification by MFI thresholds revealed amplified risks at MFI≥1,000, particularly for AMR (RR=7.51 vs 4.65 at MFI<1,000; Pinteraction<0.001) and loss of graft (RR=2.30 vs 1.81; P=.032). KT with MFI≥1,000 had the highest cumulative hazards (AMR: RR=8.12, 5.94–11.10; graft loss: RR=2.55, 1.98-3.28), whereas LT recipients with MFI≥1,000 had higher mortality RR=2.01 (1.44–2.80). Secondary outcomes included increased delayed graft function (DGF: RR=1.49, 1.12–1.98) in pre-DSA+ patients, driven by KT (RR=1.82, 1.30–2.55), but no association with T-cell–mediated rejection (TCMR: RR=1.10, 0.94–1.28). Conclusions Pre-DSAs is a strong independent predictor of AMR and graft loss in SOT, with amplified risks in KT and cohorts with DSA+ MFI≥1,000. These findings advocate for universal pretransplant DSAs screening and DSA+MFI-guided desensitization to prioritize high-risk patients. Organ-specific strategies, intensified AMR surveillance in KTs, and mortality-focused monitoring in LTs, are critical to improving outcomes.
Keywords: Preformed donor-specific antibodies, solid organ transplantation, Antibody-mediated Rejection, Graft Survival, mean fluorescence intensity, risk stratification, organ-specific risk, HLA antibodies
Received: 23 May 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Kang, Liu, Liu, Han and Li. 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: Daihong Li, Tianjin First Central Hospital, Tianjin, China
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