P101 Development of C1Q binding donor specific anti-HLA antibodies in pediatric kidney transplant recipients

HUMAN IMMUNOLOGY(2017)

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摘要
Aim De novo donor specific anti-HLA antibodies (DSA) have been associated with poor allograft outcomes in kidney transplantation. However, the value of post-transplant DSA monitoring in pediatric kidney transplant recipients is still debated. In this study, we investigated the incidence of de novo DSA, their ability to bind complement and their relationship with clinical outcomes in a population of pediatric kidney transplant recipients. Methods Serial samples of serum from 34 pediatric kidney transplant recipients without pre-transplant DSA were tested using the conventional and C1q single antigen bead assays (One Lambda/ThermoFisher). Patients were transplanted at our center from July 2009 to September 2015. All patients had negative flow crossmatches at the time of transplant. The MFI cutoff values used in the conventional and C1q assays were 1000 and 500, respectively. Typing of HLA-A, B, C, DR and DQB genes was performed by SSO. Results During the follow up interval (median 4 years), 9 (26%) out of 34 recipients developed DSA. Median time from transplant to DSA development was 12 months. At the time of detection, DSA were C1q positive in 8 of 9 patients. The mean number of C1q + DSA per patient was 2.7. Seven out of 8 patients had C1q + DSA directed to the donor HLA-DQB antigen(s). C1q + DSA persisted over time and were associated with worse graft function at 1 year ( p  = 0.004), increased incidence of antibody mediated rejection (AMR; p p  = 0.08). Despite treatment for AMR, 5 (63%) of 8 patients with C1q + DSA lost their grafts during the follow up interval. In contrast, only 2 (8%) out of 26 patients without DSA lost their graft during the same interval ( p Conclusions The incidence of de novo C1q binding DSA in our pediatric patient population is high, likely due to increased non-compliance. C1q + DSA identified patients at high risk for graft loss. These findings support the role of frequent monitoring of DSA, particularly during the first year post-transplantation, and highlight the need for prompt therapeutic intervention in patients with C1q + DSA.
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