Identification of antibodies toward private and public class I HLA epitopes in sensitized patients.

Abstract

Antibodies to HLA determinants may decrease the increment after platelet transfusion and are correlated with increased rates of rejection in renal transplantation. Cross-match tests and HLA antibody specification are used to identify compatible donors for sensitized patients. However, search for cross-match negative donors may be ineffective, and many sera containing antibodies toward public HLA epitopes give no clear results in conventional specificity analysis. We tested a series of 4,625 sera from 1,073 patients with hematological, malignant or other diseases using a fluorescence lymphocytotoxicity test (LCT). We applied an evaluation program incorporating a list of public antigens belonging to known cross-reacting groups (CREGs) to detect antibodies toward private and just as well public epitopes. In 694 sera (15.0%) from 240 patients the panel reactivity (PRA) in LCT assay was higher than 5%. PRA was > or = 50% in 258 (37.2%) and < 50% in 436 sera (62.8%). In both groups we identified specific antibodies toward public HLA class I epitopes. Overall antibody specification was successful in 429 of 694 sera (61.8%) and in 175 of 240 patients (72.9%), respectively. The rate of antibodies against public epitopes shared by more than one HLA class I gene product was 203/694 (29.3%) with respect to tested sera and 83/240 (34.5%) with respect to patients. The rate of public epitope antibodies was highest in sera with PRA values from 30 to 90% showing public epitope specificity in 159 of 353 sera (45.0%). We conclude that antibodies toward public HLA class I determinants are detectable not only in highly sensitized patients. The described program may increase the rate of antibody specification and facilitate the platelet supply in platelet refractory patients.