Donor HLA specific antibodies (DSA) can cause acute rejection and graft lost after renal transplantation. However neither the damaging antibody types, nor their acceptable levels are currently known. The aim of this research was to investigate the role of four DSA IgG subclasses in the immune response in order to identify any potentially damaging antibodies and their influence on short and long-term postoperative outcomes. Levels of pan-IgG and IgG subclasses of the DSAs were determined pre-treatment, at the day of peak pan-IgG level and at 30 day post-transplantation by single antigen microbead assay in eighty HLA-antibody incompatible kidney transplant recipients. Multivariate regression models accounting for the pan-IgG and IgG subclass levels of the DSAs and other potentially confounding patient baseline characteristics were developed to assess the risk of early rejection and graft failure. We have found that IgG4 was predictive of acute antibody mediated rejection (p=0.003) in the early post-transplant period. The multiple binary regression model and the likelihood significance analysis have shown that the occurrence of the early rejection was due to three factors: total pre-treatment IgG4 MFI levels, the highest pre-treatment MFI DSA levels and the total number of HLA mismatches. The long term graft survival times were also affected by the presence of the IgG4 in pre-treatment samples (p=0.004). Cox proportional hazard method identified 2 significant (p<0.05) factors reducing graft survival times: MFI of the highest IgG and presence of IgG4 in pre-treatment samples with the hazard ratios of 161.218 and 5.945, respectively. Thus, pre-treatment IgG4 DSA is a useful biomarker to predict and risk stratify cases with higher levels of pan-IgG DSA in HLA-antibody incompatible renal transplantation.

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