High Immunological Risk Recipients Displaying Persistent and Contiguous DSA

Abstract

The presence of HLA antibody (Ab) or donor specific Ab (DSA) pre/post transplantation (Tx) has been associated with poor renal graft outcomes. It is unclear, however, which sensitized patient will or will not experience rejection or graft loss. The purpose of our study was to try to identify recipients (recips) at greatest immunological risk for post Tx rejection and/or graft loss. Methods: We evaluated two hundred and seventy seven (277) renal allograft recips because we had sufficient pre/post Ab data on these patients. These included 23% living donor and 77% deceased-donor recips who received either Prograf, Myfortic and Pred or Cyclosporine, Rapa, and Pred treatment. Antibody mediated rejections (AMR) were biopsy confirmed and treated with Thymoglobin, Pheresis and Rituxin while cellular rejections were treated with steroids. All donor-recips were ABO compatible and transplanted following a negative donor-specific cell based flow cytometry crossmatch (FCXM) using historical and pre-Tx recip sera. Recips were risk-ranked according to whether they had or did not have HLA and/or DSA post-Tx. A subgroup of patients with persistently, contiguous (presenting at least two or more times) HLA or DSA Ab was identified. HLA Ab and/or DSA was identified using SAB (One Lambda, Inc.) and a Luminex based solid phase assay platform. Mean Fluorescence Intensity (MFI) of 1,000 was considered positive. Results: Of 277 recips undergoing renal Tx, 92 presented with no HLA or DSA post-Tx (no Ab post-Tx) while 185 recips had positive Ab post-Tx. Only 1 recip with no Ab had DSA present pre-Tx but not post-Tx. Of the 185 recips with Ab post-Tx, 31% (58/185) presented with DSA. The frequency of AMR for no Ab vs positive Ab post-Tx was significantly different 8% (7/92) vs 21% (39/185), p < 0.01 as was the three year graft survival of 92% (82/92) vs 87% (164/185), p < 0.02 for the same patients. There were 58 patients with positive post-Tx Ab that were DSA positive, however, only 39 of these recips displayed persistent and contiguous Ab and only 54% (21/39) of these lost their grafts. Moreover, 50 recips that presented with positive DSA pre-Tx would not have been considered for a donor crossmatch or transplanted using the virtual crossmatch. Conclusion: These data suggest that not all post-Tx Abs that are DSA positive result in AMR or graft loss. Recips presenting with persistent, contiguous DSA appear to be at a higher immunological risk for AMR and/ or graft loss. Finally, patients with pre-Tx DSA but who display negative donor specific cell based FCXM's can be safely transplanted.