Significant association between chronic antibody-mediated rejection and donor-specific antibodies against HLA-DRB rather than DQB in renal transplantation

Abstract

De novo production of antidonor HLA antibody has been reported to be associated with chronic antibody-mediated rejection (CAMR). However, some donor-specific antibodies (DSA) do not seem to cause graft injury. Identification of the DSA responsible for CAMR and establishment of effective screening method for early detection of CAMR are therefore essential. All sera from 586 maintenance renal transplant recipients were examined for HLA antibody using ELISA and Luminex-based assay. Positive sera were divided into high (>20% of positive control), moderate (10-20%), and low (2-10%). Donor specificities were analyzed using single antigen beads. ELISA detected only about half of high HLA antibodies (class I: n = 19, class II: n = 46) measured by Luminex-based assay. DSA against class I and class II were identified in 42% and 87% of high antibodies, respectively, including 78% against DQB and 44% against DRB. Renal dysfunction due to CAMR was closely related to high/moderate DRB DSA (n = 11), but not low DRB DSA (n = 9) nor high/moderate/low DQB DSA alone (n = 20). It was speculated that DRB DSA would be more detrimental to the graft, while DQB DSA were readily detectable in blood circulation. Further study, including detailed pathologic analysis of graft biopsy and long-term follow-up, is necessary.