Frequency of cytotoxic and helper T-lymphocyte precursors in donors with alloreactivity to recipient histocompatibility antigens. Possible use in predicting acute graft vs host disease in bone marrow transplantation
Abstract
BACKGROUND: The utility of cytotoxic T lymphocyte precursor (CTLp) and helper T lymphocyte precursor (HTLp) frequencies estimation for detecting alloreactivity and for the prediction of acute graft versus host disease (aGVHD) has been evaluated. METHODS AND RESULTS: The limiting dilution assay and a maximum likelihood statistical programme were used for CTLp and HTLp frequency estimation.
A high CTLp frequency suggesting the presence of hidden class I mismatches was detected in 41.2% of unrelated pairs. HLA-A and -B matched by serological typing and DRB1 and DQB1 matched by DNA analysis.
Severe aGVHD (grade III-IV) occurred in all patients of this group who underwent bone marrow transplantation (BMT). In two patients of the three evaluated with low pretransplant CTLp frequency a mild form (grade I) or no aGVHD developed after unrelated BMT.
Positive frequency of alloreactive HTLp was found in 50% of HLA matched unrelated pairs. The comparison of CTLp and HTLp values in the same individuals showed that these two methods are not fully alternative in detecting alloreactivity.
In the group of HLA identical siblings, 18.7% of positive HTLp results were only found. Besides HLA-DP incompatibilities, the differences in non-HLA genes could cause this alloreactivity.
CONCLUSIONS: CTLp assay has a potential for the prediction for aGVHD development following BMT from HLA matched unrelated donors. CTLp results suggest the necessity of more accurate class I typing in these cases.
The comparison of CTLp and HTLp frequencies showed that the results can differ in some unrelated donor-recipient BMT pairs suggesting the convenience of simultaneous performing of both assays for the alloreactivity assessment. More cases have to be considered to determine the relationship between pretransplant HTLp frequency and posttransplant aGVHD development in HLA identical siblings.