Selection of an unrelated donor for marrow transplantation facilitated by the molecular characterization of a novel HLA-A allele.
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.
Choo
S Y
SY
Clinical Research Division, University of Washington School of Medicine, Seattle.
Starling
G C
GC
Anasetti
C
C
Hansen
J A
JA
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005805:Genes, MHC Class I; D014644:Genetic Variation; D006086:Graft vs Host Disease / Q000209:etiology; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D006650:Histocompatibility Testing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology / Q000601:surgery; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014019:Tissue Donors
D015234:HLA-A Antigens; D004247:DNA