Detection of Donor-Specific Antibodies Both in Serum and Cardiac Allograft Biopsy in Heart Transplant Patients: Tissue DSA is More Predictive than Serum DSA

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IntroductionDonor numbers in heart transplantation (HT) rank lowest among all solid organ transplants. During the evaluation of recipients, it is crucial to distinguish sensitized patients that have antibodies with known panel reactive antibodies. These antibodies can be directed human leukocyte antigens (HLA) class-I and II. Anti HLA antibodies can detect in circulation and typing of these antibodies is also critical for the assessment of the risk of graft loss. This study aimed to: 1) discover if there was a correlation between serum DSA and tissue DSA; 2) understand the diagnostic and prognostic value of the tissue DSA.Materials and MethodsA total of 5 patients evaluated for PRA screening. Recipients of PRA >25% were accepted as sensitized patients. The Luminex assay was used for detection and typing of specific HLA antibodies both serum and protocol allograft biopsies and C1q. Protocol allograft biopsies were used for the evaluation of tissue DSA. This study was approved by Baskent University Intuitional Review Board and Ethics Committee (Project No: KA17/243) and supported by Baskent University Research Foundation.ResultsWe found a significant correlation between serum and tissue samples in regards to PRA results. When we studied solid phase assay (LUMİNEX single antigen) in 1 patient both in serum and tissue samples PRA screening were negative, 3 patients had MFI value <5000, no antibody was detected in allografts. In 1 patient that was sensitized before HT, we identified DSA (HLA*A2:01) both in circulation (MFI >10.000) and graft tissue (MFI >10.000). In the assessment of C1q, HLA*A2:01 detected both in the serum (MFI= 23.917) and graft tissue (MFI= 250) 30 days after Transplant. The pathological diagnosis of allograft biopsy that was used in the DSA assessment also showed sign of acute antibody-mediated rejection (AMR). Following plasmapheresis + IVIG +Rituximab therapy for this recipient, the value of serum anti HLA antibodies decreased (MFI<2800) and the presence of allograft DSA disappeared. Tissue DSA was not detected. DSA in graft tissue was the first to disappear in sequential studies and this was in parallel with the clinical improvement. However the reduction in serum DSA correlated with the pathological findings.ConclusionThis is the first report demonstrating DSA presence in graft tissue, albeit in 1 patient, along with response to treatment. This is a proof-of-principle study and will be supported by a larger study. Since DSA in graft tissue dictates the molecular mechanisms mediating tissue damage, monitoring DSA along with therapeutic response enable us to plan appropriate therapeutic intervention and to prevent unnecessary immune suppressive therapy for the patients.

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