Improving screening strategies for HLA-specific antibody detection in renal transplant recipients

Sensitivity in detecting low levels of alloantibodies and specificity in revealing the presence of HLA-specific antibodies are the most important clinical features of a PRA screening technique. In order to improve both aspects in revealing a pre-sensitisation status, 297 sera from 221 patients awaiting renal transplantation were screened using Amos-CDCPRA and FlowPRA class I and II beads techniques. Overall concordance was 72.7%. Moreover 48 (16.2%) serum samples showed false negative CDCPRA results and 33 (11.1%) sera presented false positive CDCPRA results. As regards the percentage of PRA positivity, we highlighted higher mean PRA levels using FlowPRA than CDCPRA technique (66%±26% vs. 37%±25%, p<0.0001). To evidence the weight of different immunising events on alloantibody production we analysed PRA results in patients receiving only one type of sensitisation (transfusion, previous transplant or pregnancy). A low incidence (4.1%) of false negative CDCPRA results was found in the group of transfused patients (Ts-group), while more false negative CDCPRA results appeared in both the re-transplants group (Tx-group 18.2%, p=0.06) and in previously pregnant female patients (Pg-group 21,9%, p=0.01). Therefore, it may not be possible to classify a patient as non sensitised solely on CDCPRA assay basis. FlowPRA data evidenced more sensitised subjects in the Tx-group (50%, p=0.0004) and in the Pg-group (34.1%, p=0.00865) than in Ts-group of patients (10.2%). We furthermore highlighted a high HLA class II positivity not only in Tx-group (55.2±33.6%) but also in Pg-group (49.8±32.6%); on the contrary it was very low in the Ts-group. From these data, FlowPRA seems to be an adequate tool for HLA-specific antibody screening in candidate renal transplant recipients able to identify patients with a high risk of poor graft outcome.