OR 47 Allele-specific antibody to hla-dq alpha chain in a case of chronic antibody-mediated rejection

Abstract

Here we present a case of chronic antibody-mediated rejection (AMR) caused by antibody to donor HLA-DQA1∗01:02. A 42 year female patient (cPRA = 97%, 1st Transplant) with ESRD 2nd to IgA nephropathy was transplanted with live donor from kidney paired donation. Flow cytometry cross matches were negative for both T and B cells with a DSA to DQB1∗06:04/DQA1∗01:02 (MFI∼5000). The MFI of One Lambda single antigen beads (SAB) are summarized in Table 1. The recipient’s self-antigen is DQB1∗06:03/DQA1∗01:03. Immunizing antigen is DQB1∗05:01/DQA1∗01:01 via pregnancy. DQB1∗06:04/09 share epitopes 85G+130Q and often react differently in from DQB1∗06:01/02/03, which share epitopes 85A+130R. Positive pattern of DQB1∗06:02/04/06 was considered unreal because it can’t be easily explained with DQB1∗ epitopes. Transplantation was preceded with Rituxan+IVIG+Plasma Plasmapheresis. Three years after transplantation, graft function has been stable; MFI for DQ6 DSA decreased to about 2000. Serial post-Transplantation biopsies showed deteriorating chronic AMR. To determine the DQ6 DSA possibly binds to transplanted kidney, eluate from biopsy was tested with SAB. In eluate, six beads with DQA1∗01:01/02 are clustered into the high end, which indicates possibly the DQ6 DSA is directed to DQ alpha chain rather than DQ beta chain. Repeating tests with Immucor SAB confirmed results from One Lambda SAB (Table 1). All positive DQ5/6 beads, including the immunizer and DSA, have DQA1∗01:01/02/04, while all negative DQ5/6 beads have self-antigen DQA1∗01:03. DQA1∗01:01/02/04 share epitopes 25Y, 41R, 129QS, while DQA1∗01:03 has 25F, 41K, 129HA. These two groups of epitopes have very distinct electro-physical properties and likely to be very immunogenic. Similar DQ6 reaction profile in SAB are found in other patients. This case highlights the importance of epitope analysis and applying multiple platform for accurately assessing immunological risk for organ transplantation.