Relevance of post-transplant HLA class I and classII antibodies on renal graft outcome

Development of HLA antibodies (Abs) specific for graft mismatched antigens is the most important factor for rejection occurrence and poor graft survival. This study was designed to characterise HLA class I and II specificity of donor-specific antibodies (DS-Abs) and to highlight the relevance of HLA specificity on renal graft outcome. We monitored DS-Abs production in 149 kidney transplanted patients (pts) for 1 year after transplantation using flow cytometry crossmatch (FCXM) and FlowPRA beads assay. Analysing graft outcome (2 years follow up), we found a higher incidence of both acute rejection and graft failure (GF) in FCXM-positive pts. than in the negative ones (ARj: 71% vs. 17.8%, p<0.00001; GF: 29% vs. 1.7%, p<0.00001). HLA specificity determination showed the production of class I and II Abs in 40% of IgG FCXM-positive pts, only class II Abs in 20% and class I alone in the remaining 40%. The analysis of class I DS-Abs specificity highlighted that 2 pts produced Abs against specificity included in recipients’ HLA CREG; one of them lost the graft during our follow up period. In the remaining pts, the Abs presented extra-CREG (9 cases) or single allelic (5 cases) specificity. As regard class II specificity only 1 patient produced Abs directed against a public antigens of the graft. Six subjects presented Abs specific for mismatched DR and/or DQ donor’s antigens and in 5 cases no specificity was defined. Correlating GF and HLA DS-Abs specificity we found that 43% of graft losses occurred in only class II DS-Abs positive pts while the remaining 57% occurred in pts showing class I only or both class I and II Abs. In conclusion our data suggests that post-transplant flow cytometric monitoring of DS-Abs allows to estimate the HLA-specific immune response in kidney transplanted pts. and emphasises the negative influence not only of HLA class I but also of HLA class II donor-specific sensitisation on renal graft survival.