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Specificity, strength, and evolution of pretransplant donor‐specific HLA antibodies determine outcome after kidney transplantation
Author(s) -
Senev Aleksandar,
Lerut Evelyne,
Van Sandt Vicky,
Coemans Maarten,
Callemeyn Jasper,
Sprangers Ben,
Kuypers Dirk,
Emonds MariePaule,
Naesens Maarten
Publication year - 2019
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15414
Subject(s) - medicine , hazard ratio , transplantation , human leukocyte antigen , antibody , incidence (geometry) , kidney transplantation , gastroenterology , donor specific antibodies , cumulative incidence , proportional hazards model , histocompatibility , cohort , immunology , urology , antigen , confidence interval , physics , optics
In this cohort study (N = 924), we investigated the evolution and clinical significance of pretransplant donor‐specific HLA antibodies (pre DSA ), detected in the single‐antigen beads assay but complement‐dependent cytotoxicity crossmatch‐negative. Donor specificity of the pre DSA (N = 107) was determined by high‐resolution genotyping of donor‐recipient pairs. We found that in 52% of the patients with pre DSA , pre DSA spontaneously resolved within the first 3 months posttransplant. Pre DSA that persisted posttransplant had higher pretransplant median fluorescence intensity values and more specificity against DQ . Patients with both resolved and persistent DSA had a high incidence of histological picture of antibody‐mediated rejection ( ABMR h ; 54% and 59% respectively). Patients with pre DSA that persisted posttransplant had worse 10‐year graft survival compared to resolved DSA and pre DSA ‐negative patients. Compared to cases without pre DSA , Cox modeling revealed an increased risk of graft failure only in the patients with persistent DSA , in the presence (hazard ratio [ HR ] = 8.3) but also in the absence ( HR = 4.3) of ABMR h . In contrast, no increased risk of graft failure was seen in patients with resolved DSA . We conclude that persistence of pre DSA posttransplant has a negative impact on graft survival, beyond ABMR h . Even in the absence of antibody‐targeting therapy, low median fluorescence intensity DSA and non‐ DQ pre DSA often disappear early posttransplantation and are not deleterious for graft outcome.