Donor specific HLA antibodies: Evaluating the risk for graft loss in renal transplant recipients with isotype switch from complement fixing IgG1/IgG3 to non-complement fixing IgG2/IgG4 anti HLA alloantibodies

HLA alloantibodies have a multitude of damaging effects on the allograft, both complement(C’) activation and Fc independent ones. To date, the clinical significance of non C’ fixing (NCF) HLA donor specific antibodies (DSA) is still unclear. In this study, we investigated whether renal transplant recipients with NCF-DSA subclasses (IgG2/IgG4,IgA1/IgA2) are at higher risk of graft loss compared to patients with exclusively C’ fixing (IgG1/IgG3). Blood samples from 274 patients were analyzed for HLA IgG and IgA subclasses using a modified single antigen bead assay. We identified 50(18.2%) patients with circulating NCF antibodies either DSA (n=17) or against third party HLA (n=33). NCF DSA were preferentially of IgG2/IgG4 isotype (11/17) and were mainly directed against HLA class II (13/17). NCF DSA were present as a mixture with strong C’ fixing IgG1/IgG3. Graft survival was similar between patients with exclusively C’ fixing antibodies and those with a mixture panel (log rang test p=0.162), and also among patients with different immunoglobulin isotype and subclasse (long rank test, p=0.732). We conclude that expansion of DSA to NCF subclasses post renal transplantation does not seem to be associated with worse graft survival as compared to the presence of exclusive C’ fixing subclasses (read more) Print this post