AUTOMATED NUCLEOTIDE SEQUENCING REVEALS SUBSTANTIAL DISPARITY BETWEENTHE HLA-A2 GENES OF BONE-MARROW TRANSPLANT RECIPIENTS AND DONORS

HLA disparity is associated with immunological complications after bon e marrow transplant and it has been demonstrated that a single amino a cid substitution can dramatically alter the function or allorecognitio n of an HLA molecule. Current serological methods for typing Class I H LA do not distinguish between most HLA-A2 variants which can differ by 1-8 amino acid residues. HLA-A2 disparity between bone marrow transpl ant patients and donors was investigated using automated nucleotide se quencing of the entire coding region of HLA-A2 genes. A total of 122 H LA-A2 alleles were sequenced from 47 patient-donor pairs (94 individua ls). HLA-A2 disparity was observed in 10 of 47 pairs (21.3%) and consi sted of HLA-A0201 mismatched with 0202 (n = 2), 0205 (n = 3), 0206 (n = 3), 0217 (n = 1) or 0221 (n = 1). Four of 6 (66.7%) non-Caucasian o r mixed race pairs were HLA-A2 disparate, while 6 of 36 (16.7%) Caucas ian pairs were HLA-A2 disparate (P = 0.008). Among all individuals HLA -A0201 was the most frequently observed allele (90.0%) while 0202 (1. 6%), 0205 (2.5%), 0206 (4.1%), 0217 (0.8%) and 0221 (0.8%) were also o bserved. This study illustrates the diversity of HLA-A2 in non-Caucasi an individuals and suggests thar HLA-A2 subtyping for applications suc h as bone marrow transplantation, especially in non-Caucasian or mixed -race donor-recipient pairs, may be important. (C) American Society fo r Histocompatibility and Immunogenetics, 1997. Published by Elsevier S cience Inc.