Immunogenicity differences between BW4 subtypes

Abstract

Aim Donor HLA-specific antibody represents a risk for rejection or engraftment failure following HLA mismatched solid organ or hematopoietic stem cell transplantation. We have examined the immunogenicity of Bw4 subtype mismatches in 211 renal recipients post-transplant. Methods HLA typing was performed using Luminex based rSSOP (LAB Type, One Lambda). HLA single antigen panels (LABScreen, One Lambda) were used to identify HLA-Bw4 sensitization. Results Bw4 epitopes present on HLA-B and HLA-A antigens can be divided into 8 subtypes based on amino acid differences at positions 77–83 (Voorter et al. Tissue Antigens, 2000). Furthermore, residues 80–83 have been shown to impact the electrostatic charge and explain observed serological Bw4 patterns (Kosmoliaptsis et al. Human Immunol. 2011). Bw4 motifs TALR and TLLR (expressed on HLA-B∗44:02, B∗13:01 and B∗37:01, B∗27:05, B47:01, respectively) have similar electrostatic potentials, but are uniquely different from the IALR Bw4 motif (expressed on HLA-B∗57:01, 58:01, 49:01, 51:01, 53:01, 15:16, 15:13, 38:01 59:01 and HLA-A23:01, 24:02, 24:03, 25:01,32:01). Previously, using serum/cell adsorption experiments, we have shown that sensitization to the IALR can occur in recipients possessing TALR or TLLR. The incidence of sensitization to these different Bw4 motifs is shown in Table 1.The IALR motif evoked the highest incidence of sensitization in recipients possessing Bw6, Bw4-TALR, or Bw4-TLLR in their own phenotype. In contrast, mismatches involving TALR or TLLR provoked little sensitization in recipients possessing IALR. Conclusions Structural and electrostatic potential differences between Bw4 subtypes appear sufficient to elicit alloimmune responses. Exposure to IALR, the most common Bw4 motif, can provoke a substantial alloantibody barrier to prospective donors (CPRA of 54%). Moreover, Bw4 sensitization may be relevant when selecting HLA allele mismatched donors for antigens that contain multiple Bw4 subtypes (i.e. HLA-B27, B38, B44, and B53). Download : Download full-size image