CYTOTOXIC T LYMPHOCYTE PRECURSOR FREQUENCIES AND HLA-C LOCUS TYPING.
S Knowles, M Diviney, L Le, C Hart, L Cantwell, R Holdsworth,
Tissue Typing ARCBS, Melbourne, Australia.
In determining the best match for a patient requiring
an unrelated allogeneic bone marrow transplant the HLA-C is sometimes overlooked.
For many years this laboratory has been performing typing by serology for
antigens Cw1 to 8 and has recently begun using PCR-SSO to type for HLA-C.
Quite often donors although matched to the patient at HLA A,B, DRB1 and
DQB1 are mismatched at HLA-C. To help determine the importance of HLA-C
matching we used PCR-SSO to HLA-C type 64 patient/donor pairs matched for
HLA-A and B by serology and for DRB1 and DQB1 by PCR-SSO. We also used
the Cytotoxic T Lymphocyte Precursor(CTLP) assay to measure the frequency
of donor derived patient reactive CTLP cells in the pairs. High frequencies
of donor derived host reactive CTLP cells have been shown to be associated
with severe GVHD. We then compared the incidence of high CTLP frequencies
in HLA-C matched pairs with that of HLA-C mismatched pairs. The CTLP assay
results showed a correlation between C locus mismatches and high CTLP frequencies.
High frequencies occured in 22 out of 25 (88%) of C locus mismatched pairs
compared with 10 out of 39 (26%) of C locus matched pairs. The greater
incidence of high CTLP frequencies in C locus mismatches highlights the
importance of C locus typing in matching, preferably using high resolution
techniques such as PCR-SSO.