A Prospective Study Analyzing the Role of Donor-Specific Endothelial Cell Antibodies in Kidney Graft Outcome: A 3-Year Follow-Up.

BACKGROUND: Rejection following kidney transplant occurs despite meticulous evaluation for the presence of HLA antibodies (Ab) by lymphocyte crossmatch and solid phase single antigen testing. This indicates that non-HLA Ab may play a role in mediating organ rejection. We have previously reported that the presence of donor-specific endothelial cell antibodies (ECA) pre transplant was not predictive of overall poorer graft outcome at one-year post living donor kidney transplant. A 3-years follow-up is now presented. METHODS: We prospectively tested 150 patients (pts) who underwent living donor kidney transplant at our center between January and December 2010, using the donor-specific endothelial XM-ONE crossmatch (42.6% female, 57.3% Caucasians, 20% AA, mean age 47 + 14.2). About 1/2 and 1/4 of patients had HLA class I and class II Ab, respectively. Pts were followed-up for three years, and we analyzed the relation of XM-ONE results to the development of rejection, proteinuria, creatinine levels and biopsy-proven vasculopathy. RESULTS: XM-ONE assay was positive in 27/150 pts (11 were IgG positive and 19 were IgM positive; 3 of these pts were IgG and IgM double positive). Among the 150 pts, at the end of the 3 years, 4 had experienced Ab mediated rejection (AMR) - only one was positive IgM XM-One; 20 experienced cellular rejection (AR), biopsy grade of 1A or greater, of whom 3 had a positive IgM XM-one and none had a positive IgG XM-One; 7 pts experienced mixed AMR and AR - of those only 1 was IgM as well as IgG positive; and 33 pts had borderline rejection (5 with positive IgM and 2 with positive IgG). We found no significant correlation between XM-ONE ab and rejection at 1, 2 or 3 years. No significant correlation between the XM-ONE results and proteinuria or creatinine levels at 1, 2 or 3 years post-transplant was observed. Anecdotally, of the 11 pts that had AMR or mixed AMR/AR, 9/11 had HLA-DSA with titer > 1:16. Of the 2 pts that had no detectable HLA-DSA, one was IgM XM-One positive and one was negative. CONCLUSION: The presence of donor-specific ECA, as determined by a positive XM-ONE IgG or IgM assay, did not show an overall association with development of acute rejection or poorer graft outcome at three years following transplant. Fewer pts had 24 month protocol biopsies potentially leading to under-reporting of sub-clinical rejection. DISCLOSURES:Friedewald, J.: Grant/Research Support, Pfizer, Stockholder, GTI.