Beneficial and detrimental human leucocyte antigen (HLA)-DR mismatches are not reflected by a differential effect of immunosuppressive drugs on the in vitro alloimmune response.
The introduction of molecular tissue typing techniques has led to an enormous increase in the number of human leucocyte antigen (HLA) alleles. This increasing polymorphism of the HLA antigens makes the selection of a well-matched unrelated donor a difficult task. Recent data suggest that some HLA mismatches are more immunogenic than others. This has led to the introduction of terms like beneficial or acceptable versus detrimental or taboo mismatches. The study considered whether the differential immunogenicity as reflected by graft survival studies can be detected in vitro as well. Mixed lymphocyte reaction (MLR) and primed lymphocyte tests (PLT) were performed with different HLA-DR mismatched combinations in the presence and absence of cyclosporine A and prednisolone. Differential effects of these immunosuppressive drugs were observed. Some reactions could easily be blocked by cyclosporine alone, whereas others need the addition of high doses of prednisolone as well before a significant inhibition was found. These differences were not only found between individual responders but also within one individual dependent on the stimulatory HLA-antigen involved. When the group of beneficial mismatches was compared with the group of detrimental mismatches, no differences were observed. Our data show that immunosuppressive drugs have a differential effect on in vitro alloimmune responses but these do not differentiate between beneficial and detrimental mismatches as defined by kidney graft survival.