C3d-Positive Preformed DSAs Tend to Persist and Result in a Higher Risk of AMR after Kidney Transplants

Abstract

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. In this study, we performed a retrospective investigation of the association of pDSAs and their C3d-binding capacity with one-year clinical outcomes. 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). 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. 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). C3d-positive pDSAs were significantly associated with a higher incidence and risk of AMR (p < 0.001, OR 94.467–188.934). 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.

La historia de un trasplante renal previo es el evento más importante para identificar subclases de IgG de los anticuerpos anti-HLA y positividad del ensayo C3d

“…25 It is also interesting to mention that for class II antibodies, 42.6% of the HLA antibodies were C3d-positive, and their median MFI was 10,341 whereas that of the C3d-negative antibodies was 1,711. 26 Sicard et al also observed a correlation between C3dbinding capacity of antibodies with a higher number and a higher MFI of DSAs. 11 Our finding regarding the SAB MFI for class II C3d positive antibodies is in agreement to the previous observations.…”

Common Data Model-based Analysis of Selective Leukoreduction Protocol Compliance at Three Hospitals

“…SOT candidates should avoid transfusion but should apply for LR blood if transfusion is unavoidable [ 16 ]. As HLA antibodies are closely related to kidney transplantation prognosis [ 17 ], we expected SLPC to be higher in kidney transplant patients than in liver transplant patients. However, as shown in Fig.…”

Role of Complement System in Kidney Transplantation: Stepping From Animal Models to Clinical Application

“…Positive C3d-binding dnDSAs were found to be associated with the presence of AMR (132,133). A study on pDSAs indicated that half of the C3d-negative pDSAs disappeared after transplantation, while all C3d-binding pDSAs persisted despite desensitization (134). Moreover, C3d-binding pDSAs were associated with a higher risk of developing AMR (134).…”

“…A study on pDSAs indicated that half of the C3d-negative pDSAs disappeared after transplantation, while all C3d-binding pDSAs persisted despite desensitization (134). Moreover, C3d-binding pDSAs were associated with a higher risk of developing AMR (134). However, the role of C1q-binding DSAs has been controversial.…”