Impact of C1q-fixing donor-specific antibodies on pancreas transplant outcomes
Ana Claudia Vidigal1, Marcelo Perosa1, Erika B Rangel2.
1Department of Abdominal Organ Transplantation, Leforte Liberdade, São Paulo, Brazil; 2Nephrology Division, Federal University of São Paulo, São Paulo, Brazil
Introduction: Donor-specific antibodies (DSA) against human leukocyte antigen (HLA) are key factors in the diagnosis of antibody-mediated rejection (ABMR). DSA are associated with allograft dysfunction, which negatively impacts the allograft survival rate after a pancreas transplant (PT). Not all DSA are equally detrimental to allograft function in the transplant setting. Therefore, the C1q complement activating ability of antibodies appears to be an important parameter to distinguish clinically inert versus detrimental DSA. This study aimed to evaluate the additional impact of C1q-binding DSA detection and clinical outcomes in PT.
Methods: All PT recipients with de novo DSA from March/2018 until July/2022 were included (N=270; being n=164 SPK and n=106 solitary[S]-PT: 90 PAK and 16 PTA). Posttransplant anti-HLA antibodies were screened by Luminex as follows: 3, 6, and 12 months or when a rejection episode occurred and twice a year thereafter for all S-PT recipients; for SPK recipients with a PRA>0 or when a rejection episode occurred at the same frequency. Patients positive for these antibodies with an MFI >500 were further screened for the C1q-fixing nature of DSA and were categorized into two groups, C1q+ DSA and C1q- DSA. We evaluate the impact of C1q-binding in ABMR, pancreas immunological graft loss, and 2-year pancreas survival.
Results: During 4.4 years of follow-up, we identified 38/270 (14%) patients with dnDSA, in PT recipients. The median time from transplantation to the first occurrence of each dnDSA was 5.5 months (1-28), mainly in the first year (84.61% SPK and 84% S-PT). C1q+ DSA were detected in 13/38 (34.2%) of PT recipients. Seven of the 13 patients (53.8%) with C1q+ DSA developed antibody-mediated rejection compared to 4 of the 21 C1q- DSA (53.8% vs 16%; p=0.024). The rate of pancreas immunological graft loss was higher in C1q+ DSA recipients (61.5% vs 16%; p=0.009) furthermore C1q+ DSA had the lowest allograft survival at 2-years (p=0.001).
Conclusion: Our study suggests that DSA with the ability to activate complement are associated with a greater risk of ABMR and immunological graft failure, as well as inferior pancreas graft survival.
