Subclass analysis of donor HLA specific IgG in antibody incompatible renal transplantation reveals a significant association of IgG4 with rejection and graft failure

Background : Donor HLA-specific antibodies (DSA) can cause rejection and graft loss after renal transplantation, but their levels measured by the current assays are not fully predictive of outcomes.
Methods : We investigated whether IgG subclasses of DSA were associated with early rejection and graft failure. DSA levels were determined pre-treatment, at the day of peak pan-IgG level and at 30 days post-transplantation in eighty HLA-antibody incompatible kidney transplant recipients using a modified microbead assay.
Results : Pre-treatment IgG4 levels were predictive of acute antibody mediated rejection (AMR) (p=0.003) in the first 30 days post-transplant. Pre-treatment presence of IgG4 DSA (p=0.008) and day 30 IgG3 DSA (p=0.03) were associated with poor graft survival. Multivariate regression analysis showed that in addition to pan-IgG levels, total-IgG4 levels were an independent risk factor for early rejection when measured pre-treatment; and the presence of pre-treatment IgG4 DSA was also an independent risk factor for graft failure.
Conclusions : Pre-treatment IgG4 DSA levels correlated independently with higher risk of early rejection episodes and medium term death censored graft survival. Thus pre-treatment IgG4 DSA may be used as a biomarker to predict and risk stratify cases with higher levels of pan-IgG DSA in HLA-antibody incompatible transplantation. Further investigations are needed to confirm our results (read more) Print this post