Specificity, strength and evolution of pretransplant donor-specific HLA antibodies determine outcome after kidney transplantation.

Authors:
Dr Aleksandar Senev, MD
Dr Aleksandar Senev, MD
KU Leuven Research and Development
PhD researcher
Leuven | Belgium
Evelyne Lerut
Evelyne Lerut
University Hospitals Leuven
Belgium
Jasper Callemeyn
Jasper Callemeyn
KU Leuven University
Ben Sprangers
Ben Sprangers
University of Leuven
Belgium
Dirk Kuypers
Dirk Kuypers
University Hospitals Leuven
Belgium
Marie-Paule Emonds
Marie-Paule Emonds
University Hospitals Leuven
Belgium

Am J Transplant 2019 May 6. Epub 2019 May 6.

Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.

In this cohort study (N=924), we investigated the evolution and clinical significance of pretransplant donor-specific HLA antibodies (preDSA), detected in the single-antigen beads assay but CDC-crossmatch-negative. Donor specificity of the preDSA (N=107) was determined by high-resolution genotyping of donor-recipient pairs. We found that in 52% of the patients with preDSA, preDSA spontaneously resolved within the first 3 months posttransplant. PreDSA that persisted posttransplant had higher pretransplant MFI values and more specificity against DQ. Patients with resolved and persistent DSA both had a high incidence of histological picture of antibody-mediated rejection (ABMR ; respectively 54% and 59%). Patients with preDSA that persisted posttransplant had worse 10-year graft survival compared to resolved DSA and preDSA-negative patients. Compared to cases without preDSA, Cox modeling revealed an increased risk of graft failure only in the patients with persistent DSA, in the presence (HR=8.3) but also in the absence (HR=4.3) of ABMR . In contrast, no increased risk of graft failure was seen in patients with resolved DSA. We conclude that persistence of preDSA posttransplant has a negative impact on graft survival, beyond ABMR . Even in the absence of antibody-targeting therapy, low-MFI DSA and non-DQ preDSA often disappear early posttransplantation and are not deleterious for graft outcome. This article is protected by copyright. All rights reserved.

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http://dx.doi.org/10.1111/ajt.15414DOI Listing
May 2019
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