HIGH FREQUENCY OF HLA-Cw AND HLA-DP INCOMPATIBILITIES IN HLA-A,B,DRB1 ALLELE LEVEL MATCHED UNRELATED DONOR-RECIPIENT PAIRS
M. Schaffer, A. Aldener-Cannavá, O. Olerup. Dept. of Biosciences at NOVUM, Karolinska Institutet and Div. of Clinical Immunology, Huddinge Hospital, Huddinge, Sweden.


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    Matching for HLA class I and II alleles is known to be important for the outcome of unrelated bone marrow transplantation. However, the precise matching requirements for the optimal clinical outcome are yet not defined. The aim of this study was to retrospectively determine allele level mismatches in a series of HLA-A,B,DRB1 matched unrelated donor-recipient pairs.
    Allele level typing for all classical HLA class I and II loci was performed by the PCR-SSP technique in 46 patients and their unrelated bone marrow donors. The criteria for donor selection were compatibility for serologically defined A and B specificities including antigen splits as well as for DRB1 alleles.
    HLA class I: Two HLA-B allele level mismatches were found. Sixteen of the 46 pairs (35%) were mismatched for HLA-Cw alleles (see Table). The frequencies of Cw incompatibilities were the same in DPB1 matched and mismatched pairs.
    HLA class II: Two DRB4, 4 DQA1, 5 DQB1, 13 DPA1 and 30 DPB1 mismatches were found.
    In contrast to previous studies we found no allele level HLA-A and few HLA-B mismatches in our group of donor-recipient pairs. This may partly be explained by our donor selection criteria. The frequency of Cw mismatches in this series was surprisingly high considering that most pairs were HLA-A and -B allele level matched. This indicates that the number of HLA class I-DRB1 haplotypes is higher than expected from A, B, DRB1 data. The high frequency of DPB1 mismatches is in agreement with previous studies and not unexpected as most HLA haplotypes do not extend to the DP subregion.
    We conclude that the high frequency of Cw mismatches in A, B, DRB1 allele level matched donor-recipient pairs shows that HLA-Cw compatibility should be directly assessed and not inferred from A, B, DRB1 compatibility.
Table:n=46

Allele level mismatch:	A= 0%	B= 4%	C= 35%	DRB1= 0%	DRB4= 4%
	DQA1= 8%	DQB1= 11%	DPA1= 28%	DPB1= 65%