Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome

Juan Molina; Ana Navas; María-Luisa Agüera; Cristian Rodelo-Haad; Corona Alonso; Alberto Rodríguez-Benot; Pedro Aljama; Rafael Solana

doi:10.3389/fimmu.2017.01310

Impact of Preformed Donor-Specific Anti-Human Leukocyte Antigen Antibody C1q-Binding Ability on Kidney Allograft Outcome

Front Immunol. 2017 Oct 31:8:1310. doi: 10.3389/fimmu.2017.01310. eCollection 2017.

Authors

Juan Molina¹, Ana Navas¹, María-Luisa Agüera^{1

2}, Cristian Rodelo-Haad¹, Corona Alonso^{1

3}, Alberto Rodríguez-Benot^{1

2}, Pedro Aljama^{1

2}, Rafael Solana^{1

4}

Affiliations

¹ Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
² Department of Nephrology, Reina Sofia University Hospital, Cordoba, Spain.
³ Department of Allergy and Immunology, Reina Sofia University Hospital, Cordoba, Spain.
⁴ Department of Immunology, Infanta Cristina University Hospital, Badajoz, Spain.

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.

Keywords: C1q-binding antibodies; allograft-loss risk; kidney allograft survival; kidney transplantation; preformed anti-HLA antibodies; single antigen beads assay.