61-OR

Abstract

Aim Complement binding donor specific HLA antibodies (DSA) detected by the C1qScreenTM assay are associated with poor post-transplant outcomes. However, in some patients with episodes of antibody mediated rejection or graft failure, C1q binding DSA are not detected by the C1qScreenTM. We have recently developed a sensitive anti-human globulin (AHG) - C1qScreenTM enhanced (ACE) assay, which detects more complement binding DSA compared to standard protocol. Here we investigate functional relevance of HLA antibodies identified using the ACE assay by correlation with CDC and CDC-AHG Lambda Cell Tray (LCT) testing. Methods Ten sera from highly sensitized post-transplant patients with well characterized HLA antibodies were tested using C1qScreenTM and the ACE assay. CDC and CDC-AHG crossmatches were performed using 1W60 LCT panels. CDC and CDC-AHG PRA were calculated (#Pos /#Valid reactions) for each serum and compared to predicted PRA values based on identified C1q positive antibody specificities. Results PRA values predicted based on ACE assay positive antibodies correlated with CDC-AHG PRA (mean difference = 2.9%, range = −1.7-8.6%) but not with CDC PRA (mean difference = 26.2%, range = 7-48%). In contrast, PRA values predicted based on C1qScreenTM positive antibodies correlated with CDC PRA (mean difference = −4.8%, range = −39.7 – 17.2%) but not with CDC-AHG PRA (mean difference = −28%, range = −62 – 5%). Importantly, 377 of 383 (98.4 %) positive CDC-AHG reactions were predicted to be positive by ACE assay. In contrast, a significant proportion of positive CDC reactions, 49 of 240 (20.4%), were not predicted positive by standard C1qScreenTM suggesting poor assay sensitivity. Conclusions Strong correlation between ACE assay positive antibodies and CDC-AHG reactivity suggests that ACE assay may be used to predict CDC-AHG crossmatches. This would be very useful in pre-transplant risk assessment especially in the context of class II HLA antibodies not easily studied with CDC/CDC-AHG methods.