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Abstract

Interpretation of HLA antibody reactivity should consider different HLA-Bw4 epitopes associated with HLA-B and HLA-A alleles. HLA typing was performed using Luminex based rSSOP (LAB Type, One Lambda) or sequence based typing (AlleleSEQR, Celera). HLA antibody testing used HLA phenotype (LIFECODES, Gen-Probe) and single antigen (LAT, One Lambda) bead panels on a Luminex platform. Bw4 is an epitope present on several HLA-A and HLA-B antigens that can be divided into 8 subtypes based on amino acid differences (Tissue Ag 2000, 56:363). Recently, residues 80-83 have been shown to influence electrostatic potential of the Bw4 epitope, explaining differences in serological patterns (Human Immunol 2011, 72:1049). We present two patients with Bw4 present in their own phenotype yet they generated antibody to a different Bw4 subtype. Patient 1 typed as a B ∗ 44:03, containing Bw4 residues 80 T -81 A -82 L -83 R . She was sensitized through pregnancy to her daughter who typed as a HLA-B ∗ 27:02 containing Bw4 residues 80 I -81 A -82 L -83 R . This daughter was a potential HLA mismatched stem cell donor. Patient 2 was a renal patient who typed as a HLA-B ∗ 37:01 containing Bw4 residues 80 T -81 L -82 L -83 R . This patient was sensitized to HLA-B51 and -B53, both contain Bw4 residues 80 I -81 A -82 L -83 R . Patient 2 is being evaluated for retransplantation. For both patients, the strongest antibody reactivity was toward beads containing the Bw4 motif 80 I -81 A -82 L -83 R , to which they were both sensitized. Moreover, there were differences in antibody strength toward HLA antigens that differed only by the 80 I -81 A -82 L -83 R epitope (B49 vs B50 and B38 vs B39). Cell adsorptions are underway to confirm the presence of Bw4 subtype-specific antibodies. Sensitization to Bw4 subtypes may be relevant when selecting HLA allele mismatched donors for antigens that contain multiple Bw4 subtypes. Accurate characterization of antibody specificity permits identification of incompatible alleles not represented on HLA bead panels.