Precise HLA typing is crucial in the selection of marrow donors for the treatment of patients with
hematologic malignancy. This study was undertaken to characterize an unusual variant of
HLA-A30, designated HLA-A30JS, identified in a patient with
leukemia who was a candidate for unrelated donor marrow
transplantation. IEF and
cDNA-sequencing analyses revealed that A30JS is a novel variant differing from the IEF-defined subtype A30.1 (encoded by the A*3002 allele) by a single amino acid substitution. An unrelated marrow donor was identified who was matched with the patient for
HLA-A3, B7, B18, DR2, and DR3, but mismatched within the A30
antigen family for the two distinct alleles A*3002 versus A30JS. These two alleles encode a single amino acid substitution, Arg versus Gly, at position 56 in the alpha 1 domain. Position 56 is located outside the
antigen-binding cleft of the class I molecule, suggesting that this substitution may not be functionally significant.
Transplantation from this donor was performed and the patient is surviving free of
leukemia for more than 700 days after transplant. The maximum acute GVHD observed was scored as grade II, but immunosuppressive therapy is still required for control of chronic GVHD. This study demonstrates how the molecular characterization of a novel
HLA-A allele in a patient could facilitate the selection of an unrelated donor. Lacking this information, it would not have been possible to select a donor for this patient, and thus apparently successful marrow transplant could not have occurred.