Mean fluorescence intensity evolution is a more sensitive predictor than simple positivity of posttransplant donor-specific antibodies in pancreas transplantation outcomes
Ana Claudia Vidigal1, Fernanda Danziere1, Renato De Marco2, Marcelo Perosa1.
1Department of Abdominal Organ Transplantation, Leforte Liberdade, São Paulo, Brazil; 2Immunogenetic Institute and Research Incentive Funding Association, São Paulo, Brazil
Introduction: Donor-specific antibodies (DSA) against human leukocyte antigen (HLA) are key factors in the diagnosis of antibody-mediated rejection (ABMR) and related to allograft dysfunction, which negatively impacts the allograft survival rate after pancreas transplant (PT). However, no study has compared the simple positivity of posttransplant DSA and MFI evolution over time after pancreas transplantation.
Methods: From March/2018 until July/2022 we evaluated the sera of 270 PT recipients (164 SPK and 106 solitary[S]-PT: 90 PAK and 16 PTA). All PT recipients with de novo DSA were included. 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 were considered positive for these antibodies with an MFI >500. De novo DSAs were categorized in two groups, according to MFI evolution: MFI increase ≥ 50% or stable MFI (increasing or decreasing ≤ 50%) versus MFI decrease ≥ 50% or dnDSA disappearance. We evaluate the course of MFI evolution in acute rejection, pancreas immunological graft loss and long-term pancreas survival.
Results: During 4.4 years of follow-up, we identified 38 patients with dnDSA, which accounts for 14% of the total population of 270 PT recipients. Among the 38 patients with dnDSA, 19/38 (50%) had increased or stable MFI over time and the other 50% showed decreased MFI or disappeared dnDSA. The median number of DSA collections per patient was 2.4, but 36.6% of patients had ≥4 tests performed. The average 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). More rejection episodes were observed in patients with increased or stable MFI (19[100%] vs 12[63.2%], p=0.008), and the rate of pancreas immunological graft loss was higher (p<0.0001) in this group. ABMR occurred in 11/38(21%) and graft loss in 5/11(62.5%) of recipients with ABMR, especially in patients with both class I and II dnDSA, and those with multiple dnDSA. Comparing both groups, more ABMR episodes occurred in patients with increased or stable MFI (9[81.8%] vs 2[18.2%], p=0.029). In the group with dnDSA disappearance or MFI decrease ≥ 50% at some point during follow-up, there was better long-term pancreas survival (p<0.0001).
Conclusion: Our study suggests that the persistence or increase of MFI dnDSA posttransplant has a negative impact on allograft survival and describes a relevant number of patients with a stable disappearance or decrease of dnDSA, which is related to better allograft survival.
