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A transplantation patient who is not presensitized to any HLAs receives a 5/6 matched allograft. The typing results are as follows:

Patient: HLA-A2, -A3, -B7, -Bx, -DR7, -DR11

Donor: HLA-A2, -A3, -B7, -B27, -DR7, -DR11

The patient develops de novo alloantibodies detected on routine serum monitoring on 50% of a panel of cells (panel reactive antibody [PRA] ~50%). Solid-phase assays (SPAs) using individual human leukocyte antigen (HLA)-coated beads show antibodies reacting with over 20 HLA-B specificities, including HLA-B27. The serum also shows positive reactions against HLA-A23, -24, -25, and -32. The patient’s medical history records no other sensitizing events other than the transplant. Which one of the following is the best explanation?

The patient produced donor-specific antibodies to a likely mismatched allele of HLA-A2 (which is present in about 40% of the population) not represented on the SPA beads but cross-reacts with multiple HLA-A and -B alleles. The patient produced multiple anti-HLA antibodies against mismatched, nontyped loci (HLA-C, -DQ, -DP), which cross-react with multiple HLA-A and -B alleles. The patient produced antibodies against the β-2 microglobulin chain of HLA class I expressed by half of the cell panel and used by all the HLA alleles identified by SPAs. The patient produced a single antibody against the epitope Bw4 present in HLA-B27 and many HLA-A and -B alleles.

Show Diagnosis/Topic

• There are several epitopes common to many human leukocyte antigen (HLA) alleles. These are often referred to as “public epitopes.”

• The Bw4 antigen consists of four amino acids at positions 80-83 in HLA class I molecules. It is present on alleles HLA-B5 (51, 52, 5102, 5103), 0802, 0803, 13, 17 (57, 58), 1809, 27, 37, 38 (16), 44 (12), 47, 49 (21), 53, 5607, 59, 63, 67, 77, and HLA-A23, 24, 25, 32.

• The Bw6 epitope consists of 4 amino acids: NLRG 80-83 at positions 80-83 in HLA class I molecules. It is present on alleles HLA-B7, 703, 8, 1309, 18, 2708, 2712, 2718, 35, 39 (16), 3901, 3902, 4005, 4406, 4409, 45 (12), 46*, 4702, 48, 50 (21), 54 (22), 55 (22), 56 (22), 60 (40), 61 (40), 62 (15), 64 (14), 65 (14), 67, 71 (70), 72 (70), 73, 75 (15), 76 (15), 78, 81.

• Only a handful of HLA-B alleles have neither Bw4 nor Bw6 (HLA-B1806, -B4601, -B5503, and -B7301).

• A transplant recipient who has only one Bw epitope can form antibodies against the other Bw epitope.

• Bw4/6 antibodies can have a major impact on the donor pool available to the presensitized patient.

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Clinical Pathology: General Principles, Immunology & Histocompatibility

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