Association of donor-specific antibodies with adverse outcomes in solid organ transplantation: A systematic review and meta-analysis of 69 studies.

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.