Mismatched unrelated donor transplantation
SEMINARS IN HEMATOLOGY
Authors: Petersdorf, Effie W.
Abstract
There are now more than 25 million volunteer donors registered worldwide for patients in need of a life-saving hematopoietic cell transplant to cure blood disorders. Although a human leukocyte antigen (HLA)matched donor remains the preferred stem cell source for transplantation, the use of a donor with limited HLA mismatching may be considered. Significant advances in clinical and basic research have been instrumental in furthering the understanding of donor-recipient HLA mismatches that are better tolerated than other mismatches. An increased appreciation of the role of regulatory region variation that affects the level of HLA expression provides new approaches for the selection of HLA-mismatched donors. (C) 2016 Elsevier Inc. All rights reserved.
A simple electronic tool for assessing amino acid sequence polymorphisms within exon-2 of HLA-DPB1 alleles
HUMAN IMMUNOLOGY
Authors: Sullivan, H. Clifford; Gragert, Loren; Smith, Geoffrey H.; Lindblad, Kelsi; Gebel, Howard M.; Bray, Robert A.
Abstract
In November 2014, the OPTN/UNOS Board of Directors mandated that HLA-DPB1 typing be performed for all deceased donors. Currently, there are over 1,000 known HLA DPB1 alleles, yet fewer than 30 are represented on commonly used single antigen bead (SAB) solid phase antibody assays. Moreover, the official World Health Organization (WHO) nomenclature for the DPB1 locus does not permit assessment of structural relationships between alleles based on their names. Thus, for donor DPB1 alleles lacking a corresponding SAB, determining the compatibility between a donor-recipient pair when the recipient possesses DPB1 antibodies currently requires the use of manual sequence alignments. Multiple studies have reported that DPB1 alleles can be classified into serological-defined categories based on shared protein sequence motifs residing in distinct hypervariable regions. To date, six such motifs have been recognized. To address this problem, we developed a computer-assisted tool to compare donor and recipient DPB1 allele sequences, specifically those defined by DPB1 hypervariable region motifs located in exon 2 (http://dpreport.hlatools.org). This tool quickly identifies mismatched DPB1 motifs, and easily permits the identification of motif-based donor-specific antibodies (DSA) to DPB1.