The probability of HLA-C matching between patient and unrelated donor at the molecular level: estimations based on the linkage disequilibrium between DNA typed HLA-B and HLA-C alleles.
BACKGROUND
Recent evidence suggests a more significant role of HLA-C as a target of alloreactions after bone marrow transplantation than previously suspected. Although linkage disequilibrium (LD) between HLA-B and -C serogroups is well documented, the level of LD at the allelic level is not known. In this study, we determine the LD between HLA-B and -C alleles and estimate the probability of molecular HLA-C matching between unrelated individuals who match for both HLA-B alleles.


METHODS
The study included 727 haplotypes from 849 individuals who were HLA-A, -B, -C and -DRB1 typed by high-resolution PCR-SSOP technique. Zelterman's statistic was used to test for global LD between HLA loci. LD between specific HLA-B and -C allelic combinations was calculated from their observed and expected frequencies in the study haplotypes. The probability of HLA-C matching for specific HLA-B allele was estimated from contingency table generated from the HLA-B and -C haplotypes.


RESULTS
HLA-C was found to exist in LD with HLA-A and -B, as well as -DRB1, loci; however, it was strongest between HLA-B and -C loci. A marked variability in the level of LD between specific HLA-B and -C alleles was noticed. A strong LD was seen in some allele pairs like B*0702-C*w0702, B*3501-Cw*0401, and B*0801-Cw*0701. The overall estimated probability of HLA-C matching between unrelated individuals that match for both HLA-B alleles is 42.25%. For 237 (72.9%) of 325 combinations involving the 25 commonest HLA-B alleles, the estimated probability that the HLA-B-matched unrelated individuals will match for both HLA-C alleles is less than 50%. In addition, a 100% probability of matching for both HLA-C alleles is expected only if both individuals bear either B*0801/ B*0801 or B*4901/B*4901 or B*0801/B*4901. Probability tables for common alleles are presented.


CONCLUSIONS
We conclude that, despite matching for both HLA-B alleles by high resolution DNA typing and the presence of a strong LD between HLA-B and HLA-C loci, unrelated individuals are more likely to mismatch rather than match for one or both HLA-C alleles.
Prasad
V K
VK
Department of Pediatrics, Biochemical Immunogenetics Laboratory, Memorial Sloan Kettering Cancer Center, New York 10021, USA. prasadv@mskcc.org
Heller
G
G
Kernan
N A
NA
O'Reilly
R J
RJ
Yang
S Y
SY
D000483:Alleles; D016026:Bone Marrow Transplantation; D004247:DNA / Q000032:analysis*; D005787:Gene Frequency / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D015810:Linkage Disequilibrium / Q000276:immunology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011336:Probability; D014019:Tissue Donors
D015235:HLA-B Antigens; D015236:HLA-C Antigens; D004247:DNA