Dispermic chimerism identified during HLA typing for stem cell transplantation

Abstract

Chimerism is defined as the presence of two genetically distinct cell populations in an organism. Few cases of phenotypically normal dispermic chimeras have been reported and most showed abnormalities on blood typing. A 32-year-old man was diagnosed with acute myelomonocytic leukemia. He clearly typed as group A, D-. No abnormalities of sexual development were identified on multiple physical exams, previous exploratory surgery, or CT scans. Molecular HLA typing (sequence-specific primers) in preparation for stem cell transplant showed the patient to have three HLA-B* and three HLA-Cw* alleles. Initial serologic HLA typing reported two haplotypes, but on subsequent review reactions for a third HLA-B antigen that were initially deemed to be false-positive reactions were identified. Two of 10 microsatellite short tandem repeat (STR) loci also showed three distinct alleles in blood and buccal samples. In all studies the third allele was attributable to a dual paternal contribution. This case represents dispermic chimerism, with one maternal and two paternal haplotypes variably distributed throughout body tissues in a phenotypically normal man without abnormalities in blood typing. The presence of additional alleles that may have been undetected or dismissed by serologic typing should be carefully investigated and verified by molecular techniques. Molecular HLA typing may increase the accurate identification of phenotypically normal chimeras and aid in selecting proper donors for transplantation to reduce graft-versus-host disease and transplant rejection in these patients.