Severe acute graft-vs-host disease in a patient with acute monocytic leukemia having a recombination event between HLA-A/B loci from a multiple recombinant family.
Human leukocyte antigen (HLA) recombination, particularly multiple recombinations can produce novel haplotypes, thereby complicating donor-recipient selection and possibly inducing severe graft-vs-host disease (GVHD) after nonfully matched allogeneic hematopoietic stem cell transplantation. Here, we report for the first time that a 30-year-old female acute monocytic leukemia patient with an HLA-A/B recombinant haplotype, who has three unmatched and one HLA-B/DRB1 recombinant haplotype siblings, presented grade IV acute GVHD (aGVHD) after transplantation from a sibling with a single allele only mismatch at the classical HLA-A locus. Furthermore, using a new three-dimensional structure modeling application, we inferred that the structural differences in peptide-binding and T-cell receptor interaction sites can significantly change the immunogenicity of mismatched HLA molecules, potentially one of the main causes of aGVHD.
Sun
Y
Y
Department of Immunology and National Center for Biomedicine Analysis, Beijing 307 Hospital Affiliated to Academy of Medical Sciences, Beijing, China.
Kong
F
F
Ren
S
S
Yuan
F
F
Liang
F
F
Liu
N
N
Jin
L
L
Xi
Y
Y
D000328:Adult; D019943:Amino Acid Substitution; D005190:Family; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics*; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D008958:Models, Molecular; D010375:Pedigree; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic; D012307:Risk Factors
D015234:HLA-A Antigens; D015235:HLA-B Antigens