Role of Non-Donor Specific HLA Antibodies (NDSA) in Kidney Transplant Rejection.

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Kidney transplant course is often complicated with development of Donor Specific Antibody (DSA) which have been associated with antibody-mediated rejection (ABMR) and poor allograft survival. However the role of Non-Donor Specific Antibody (NDSA) in occurrence of graft rejection and loss remains controversial. We studied patients who received a kidney transplant at Harper University Hospital from 2000-2010 and grouped them based on development of antibodies. The sera of patients were routinely screened for DSA and NDSA at 6 month to one year of transplant via ELISA or Luminex assay and only those with MFI >2500 were considered positive. The patients were evaluated for occurrence of biopsy proven acute rejection which was classified as cellular or ABMR per Banff criteria. Graft function was determined by most recent blood creatinine levels as of 12-31-2012 and graft loss was defined as need to return to dialysis or re-transplant and was censored for death. Of the 200 patients included in the study, 63 (31.5%) had NDSA only, 10 (5%) produced DSA only, 25 (12.5%) produced both and 102 (51%) non-producers at an average of 7.9 months post-transplant (range: 1-18 months). The baseline recipient characteristics were comparable except that recipients producing NDSA only or both were more likely to have had a previous transplant and therefore had higher peak PRA than non-producers and DSA only, which is suggestive of preformed NDSA due to prior sensitization. Those who produced both were more likely to be on maintenance steroid as compared to non-producing, NDSA only, and DSA only (12% vs. 32.35%, 22.22%, and 30% respectively; p<0.05). The fraction of patients with greater strength of DSA and NDSA i.e. MFI >10K was higher in the combined group than those in NDSA only (80% vs. 51.28%; p=NS) and DSA only (66.7% vs. 0%; p<0.05). There was an increased incidence of ABMR in those who produced both as compared to non-producers, NDSA only, and DSA only (20% vs. 3.92%, 1.59%, 0% respectively; p<0.01), while there was no difference in cellular rejection rates among the groups (p=NS). While the serum creatinine at last follow-up was not different between the groups, the graft loss was higher in those that produced both than others. In conclusion, NDSA alone especially at MFI <10K are not associated with increased risk of ABMR or graft loss. It is unclear if higher levels of NDSA are detrimental, especially in presence of DSA.