Abstract

Unacceptable HLA antigens are largely determined by testing sera with Luminex single antigen (LSA) beads. Table 1 shows the MFI values for the five DQB7 beads in three pre-transplant specimens performed on a patient with a cPRA of 99%. DQA1*05 and DQA1*06:01, but not DQB7, were listed as unacceptable antigens. A deceased donor with DQA1*01,03 and DQB5,7 became available and was virtual and flow cytometry crossmatch compatible. On post-op day 14, the patient presented with graft dysfunction. A biopsy contained evidence of antibody mediated rejection (AMR), which was supported by microarray. A donor specific antibody (DSA) screen revealed a greater than 10-fold increase in the previously negative DQB7 beads (DQA1*02:01/DQB1*03:01 and DQA1*03:01/DQB1*03:01) in addition to the previously positive DQA1*05:03, DQA1*05:05, and DQA1*06:01 beads and was consistent with a DSA to DQB7. C1q testing was positive for DQA1*05 only, which was not donor specific. The patient was aggressively treated for AMR but a repeat biopsy on post-op day 25 contained a thrombotic microangiopathy consistent with AMR. The allograft was removed on post-op day 75 due to non-function. Investigation into this case revealed a previous failed transplant with a DQB7 positive donor at another institution, which was unknown to our laboratory. Although the DQA1* typing was not available for the first donor, DR/DQB linkage analysis favors DQA1*05 consistent with the pre-transplant LSA and post-transplant C1q results. Based upon the clinical course, we hypothesize DQB7 specific memory B cells, formed in response to the first donor, facilitated accelerated AMR, which may have been avoided by listing DQB7 as an unacceptable antigen. In conclusion, the results of the LSA assay are only one component of the patient’s immunological profile. Decisions regarding the listing of unacceptable antigens must additionally take into consideration previous immunizing events, like a failed transplant, and this information must be provided to the histocompatibility laboratory for optimal patient care.

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