Abstract
The consolidation of single antigen beads (SAB-panIgG) assay in the detection of preformed anti-human leukocyte antigen (HLA) antibodies has improved transplantation success. However, its high sensitivity has limited the allograft allocation for sensitized patients, increasing their waiting time. A modification of the standard SAB-panIgG assay allows the detection of that subset of antibodies capable of binding C1q (SAB-C1q assay). However, the clinical usefulness of SAB-C1q assay for determining the unacceptable mismatches is under discussion. We retrospectively analyzed the impact of preformed donor-specific anti-HLA antibodies (DSA) according to the C1q-binding ability on allograft outcome, examining 389 single-kidney transplanted patients from deceased donors. Recipients with preformed C1q-binding DSA showed the lowest allograft survival up to 7 years (40.7%) compared to patients with preformed non-C1q-binding DSA (73.4%; p = 0.001) and without DSA (79.1%; p < 0.001). Allograft survival rate was similar between patients with preformed non-C1q-binding DSA and patients without preformed DSA (p = 0.403). Interestingly, among the high-mean fluorescence intensity DSA (≥10,000) population (n = 46), those patients whose DSA were further capable of binding C1q showed a poorer allograft outcome (38.4 vs. 68.9%; p = 0.041). Moreover, in our multivariate predictive model for assessing the risk of allograft loss, the presence of C1q-binding DSA (HR 4.012; CI 95% 2.326–6.919; p < 0.001) but not of non-C1q-binding DSA (HR 1.389; CI 95% 0.784–2.461; p = 0.260) remained an independent predictor after stratifying the DSA population according to the C1q-binding ability and adjusting the model for other pre-transplantation predictive factors including donor age, cold-ischemia time, and HLA-DR mismatches. In conclusion, the unacceptable mismatch definition according to the SAB-C1q assay would improve the risk stratification of allograft loss and increase the limited allograft allocation of highly sensitized patients, shortening their waiting time.
Highlights
The presence of preformed antibodies against human leukocyte antigen (HLA), and against those antigens expressed by the organ donor, is strongly associated with an increased risk of rejection and premature allograft failure [1]
The entire population (n = 389) was stratified into two groups according to the presence or absence of preformed donor-specific anti-HLA antibody (DSA) retrospectively detected by the standard single antigen beads (SAB)-panIgG assay
Regarding the increased risk for developing anti-HLA antibodies, patients belonging to the DSA+ group had a higher panel reactive antibody (PRA) by complement-dependent cytotoxicity (CDC) at time of transplantation (21.7 vs. 2.2; p < 0.001)
Summary
The presence of preformed antibodies against human leukocyte antigen (HLA), and against those antigens expressed by the organ donor (donor-specific anti-HLA antibodies, DSA), is strongly associated with an increased risk of rejection and premature allograft failure [1]. Against this background, the identification of antibody specificities in recipients awaiting solid organ transplantation has become a worldwide indispensable clinical practice to accurately assign their unacceptable HLAantigen mismatches [2]. Many highly sensitized patients, with poor clinical prognosis, could die while waiting for a suitable donor
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