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The 'HLA conundrum in bone marrow transplantation': correct interpretation of anti-HLA antibodies in haploidentical donor selection

Bone Marrow Transplantation volume 52, pages 902–904 (2017)Cite this article

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Matching donor and recipient for HLA class I (-A, -B and -C) and class II (-DRB1 and -DQB1) haplotypes is a key part of successful allogeneic hematopoietic stem cell transplantation (AHSCT). Currently there are almost 14 500 HLA alleles, which is up from 12 000 alleles 2 years ago and despite the expansion of worldwide unrelated donor registries, the chances of finding a phenotypically matched unrelated donor vary, from 75% for Caucasians to under 20% for ethnic minorities.1 This has led to the emergence of alternative options with less stringent requirements for HLA matching like umbilical cord HSCT (UCBT) and haploidentical HSCT. However, it is vital to screen for the presence of anti-HLA antibodies especially for antibodies directed against the donors-mismatched HLA antigen or donor-specific antibodies (DSAs). The role of DSAs in solid organ transplant rejection is well known.2 In AHSCT, DSAs have been associated with primary graft failure after either an 8/8-matched-unrelated AHSCT or UCBT. In haploidentical transplants, 75% of patients with DSAs with median fluorescent intensity >1500 failed to engraft.3 With the increasing use of haploidentical donors, the presence of preformed DSAs will play a vital role in graft survival.

DSAs were initially tested using a complement-dependent microlymphocytotoxicity assay4 described in 1968, and was the standard internationally recognized method for detection of anti-HLA antibodies for 30 years. Subsequently solid-phase assays (SpA) were introduced wherein anti-HLA antibodies were identified by detecting their binding to HLA peptides immobilized on a solid surface. The current fluorescence-based SpA is able to concurrently distinguish up to 100 different microparticles or beads. Each bead contains a single HLA antigen and the beads contain a unique ratio of different fluorochromes that provide a distinctive signal that is recognized by Luminex technology.5 The patient’s serum is incubated with the beads and a fluorescent-conjugated anti-human IgG binds to alloantibody bound to its antigenic target. The output referred to as mean fluorescence intensity (MFI) is considered as a semi-quantitative measure of the amount of antibody present. These methods have increased the number of transplant candidates recognized to have lower levels of preexisting sensitization. Using these techniques, the rates of sensitization range from 20 to 40% of patients with any HLA antibodies and up to 24% of patients with DSA.3, 6, 7, 8, 9, 10, 11 Limited donor options and /or an urgent need to proceed to transplant have led physicians to attempt various means to lower DSA to levels that would permit successful donor stem cell engraftment.6, 11, 12, 13, 14 Current practice is to screen all recipients with HLA mismatch for DSAs and consider their significance if the titers are >1000 MFI. Even though SpA is the most sensitive method for detection of HLA antibody, it has limitations, which include antigen coverage, false-positive results due to phenomenon like antibody to denatured form of antigen and false-negative results due to prozone phenomenon. Here we present a case of unique DSA prototype detected by Luminex SpA to a haploidentical donor that was also shared with the recipient, in other words a self antibody which is a case of clinical conundrum.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA,

    A L Dias, S Hashmi & W Hogan

  2. Division of Transfusion Medicine, Mayo Clinic, Rochester, MN, USA

    N Baig, L Wakefield, J Kreuter & M J Gandhi

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  1. A L Dias
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  2. S Hashmi
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Correspondence to M J Gandhi.

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Dias, A., Hashmi, S., Hogan, W. et al. The 'HLA conundrum in bone marrow transplantation': correct interpretation of anti-HLA antibodies in haploidentical donor selection. Bone Marrow Transplant 52, 902–904 (2017). https://doi.org/10.1038/bmt.2017.13

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