Case report illustrating transplant decision making based on assessing clinical relevance of apparent donor specific antibodies, allele specific antibodies, and shared epitope patterns

Abstract

Patient 36 yo WM, IgA nephropathy. LABScreen SA beads (SAB): anti-B∗44:02 (MFI = 3685), B∗44:03 (496). Quarterly testing: anti-B∗44:02 (3685-5482), B∗44:03 (121–1065). Other Class I antibodies had lower MFI; expected epitope pattern absent. No significant Class II antibodies. Donor expresses B∗44:02. At transplant: anti-B∗44:02 (5411), B∗44:03 (1065). Positive virtual-XM predicted; flow-XM negative. CDC-XM: negative. Subsequent assays: Lambda Antigen Trays: no anti-B44 detected. C1q and iBeads: negative for anti-B∗44:02 (1 and 0, respectively) and B∗44:03 (1 and 0, respectively). Flow- and CDC-XM with 3 surrogates expressing B∗44:02: all negative. The results suggest that anti-B∗44:02 does not activate complement, and would not be expected to result in humoral rejection. iBeads detect anti-HLA antibodies binding to HLA in the “native-conformation”, as would be expected to be expressed on cell surfaces. The lack of detection with iBeads further supports that the anti-B∗44:02 found by routine SAB was directed against denatured/partially-denatured antigen. Further, the expected epitope pattern was absent. Thus, this putative allele-specific antibody (ASA) anti-B∗44:02 antibody would be predicted to have no clinical relevance, similarly so for anti-B∗44:03. The patient is currently greater than 2 years post-transplantation with stable renal function, and no signs of AMR. Post-transplant SAB continue to detect anti-B∗44:02 and B∗44:03; however continue to be essentially absent by C1q or iBeads assays. This case emphasizes that potential DSA/ASA should be carefully scrutinized for the ability to activate complement and expected shared patterns of epitopes, as discriminators of potential clinical relevance. Additional testing beyond routine SAB will likely be required to assess these issues. Conclusions (1) The “stringent” use of the “virtual XM” may exclude XM-compatible donors due to “apparent” DSA. (2) Additional testing should be considered to determine whether DSA can activate complement. (3) The “extended” non-DSA anti-HLA pattern should be evaluated for the expected shared epitope patterns. (4) Further testing should be considered for discriminating antibodies to denatured vs native-conformation. (5) The Flow-XM remains the “gold standard” for making the final decision to transplant. T. Harville: Scientific/Medical Advisor; Company/Organization; Baxter Healthcare, CSL Behring. 7. Other (Identify); Company/Organization; Medical Board of Arkansas Regional Organ Recovery Agency.