Of the 560 adult recipients who underwent KT between January 2013 and July 2017 at the Samsung Medical Centre, Seoul, Korea, 455 patients (279 men and 176 women) were included in this study. In this study, we considered all of the DSAs produced within one month following KT as pDSAs and then investigated the production of pDSAs in pre- and post-transplantation and evaluated their effect on the occurrence of acute rejection and clinical outcome associated with their C3d-binding activity. Therefore, we thought that DSAs that were found only before KT should not be defined as pDSAs. They suggested that no dnDSA was detected prior to 6 months when using two strict definitions: (1) all historic and current samples were DSA-negative, with an MFI cut-off of 300 and special attention to grouped epitopes (2) no AMR in protocol biopsies at 6 months after transplantation. suggested that false-negative pDSAs and their increased titer after transplantation, due to memory B cell activation, may create the false impression of de novo DSA (dnDSA) early post-transplantation.
The titer of those cryptic antibodies can be elevated by immunological memory response shortly after KT. Human leukocyte antigen (HLA) antibodies at a titer below the SAB assay cut-off level or diluted across multiple beads that share target epitopes may not be appropriately detected in SAB assays. Identification of the C3d-binding activity of pDSAs before and early after KT is important for predicting the persistence of pDSAs and the risk of AMR induced by the presence of pDSAs. C3d-positive pDSAs were significantly associated with a higher incidence and risk of AMR ( p < 0.001, OR 94.467–188.934). Approximately half of the C3d-negative pre-pDSAs (37/73, 50.7%) disappeared after transplantation however, all C3d-positive pre-pDSAs (8/8, 100%) persisted after transplantation despite desensitization ( p = 0.008). Of 455 adult KT recipients, pre-pDSAs and post-pDSAs were found in 56 (12.3%) and 56 (12.3%) recipients, respectively, and C3d-positive post-pDSAs were found in 13 recipients (2.9%) in total. pDSAs were defined as donor-specific antibodies (DSAs) that were produced before kidney transplants (KTs) (pre-pDSAs) or within the first four weeks after KTs, owing to rebound immune response (post-pDSAs). In this study, we performed a retrospective investigation of the association of pDSAs and their C3d-binding capacity with one-year clinical outcomes. C3d-binding assays have been introduced as methods for the prediction of the presence of complement-binding functional antibodies however, the prognostic value of C3d-positive preformed donor-specific antibodies (pDSAs) has not been fully evaluated.
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