Clinical Relevance of Pretransplant Donor-Specific HLA Antibodies Detected by Single-Antigen Flow-Beads

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Abstract

Background.

Defining the clinical relevance of donor-specific HLA-antibodies detected by single-antigen flow-beads (SAFB) is important because these assays are increasingly used for pretransplant risk assessment and organ allocation. The aims of this study were to investigate to which extent HLA-DSA detected by SAFB represent a risk for antibody-mediated rejection (AMR) and diminished allograft survival, and to define HLA-DSA characteristics predictive for AMR.

Methods.

In this retrospective study of 334 patients with negative complement-dependent cytotoxicity crossmatches, day-of-transplant sera were analyzed by SAFB, HLA-DSA determined by virtual crossmatching, and the results correlated with the occurrence of AMR and allograft survival.

Results.

Sixty-seven of 334 patients (20%) had HLA-DSA. The incidence of clinical/subclinical AMR at day 200 posttransplant was significantly higher in patients with HLA-DSA than in patients without HLA-DSA (55% vs. 6%; P<0.0001). Notably, 30/67 patients with HLA-DSA (45%) did not experience clinical/subclinical AMR. Death-censored 5-year allograft survival was equal in patient without HLA-DSA and patients with HLA-DSA but no AMR (89% vs. 87%; P=0.95), whereas it was 20% lower in patients with HLA-DSA and AMR (68%; P=0.002). The number, class, and cumulative strength of HLA-DSA determined by SAFB, and prior sensitizing events were not predictive for the occurrence of AMR.

Conclusions.

These results support the utility of SAFB for pretransplant risk assessment and organ allocation, and suggest that improvement of the positive predictive value of HLA-DSA defined by SAFB will require an enhanced definition of pathogenic factors of HLA-DSA.

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