Clinical relevance of pretransplant donor-specific HLA antibodies detected by single-antigen flow-beads

Patrizia Amico, Gideon Hönger, Michael Mayr, Jürg Steiger, Helmut Hopfer, Stefan Schaub
Transplantation 2009 June 15, 87 (11): 1681-8

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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