Characterization of HLA class I specific antibodies by ELISA using solubilized antigen targets: II. Clinical relevance

Until recently, the nature of humoral sensitization to HLA has been charact erized by data from lymphocyte-based assays, predominantly cytotoxicity tes ts. We have examined the characteristics, determined by enzyme-linked immun osorbent assay (ELISA), of sera from 191 subjects known to have produced HL A-specific antibody, We found that ELISA detected higher frequencies compar ed with cytotoxicity of many (74.5%), but not all, HLA-specific antibodies; in many cases (42.6%) che frequencies of these antibodies were higher than predicted from population frequencies whereas some antibodies (23.4%) occu rred with lower than expected frequencies. Some of the increase in frequenc ies can be accounted for by crossreaccivity, i.e., sensitization to epitope s shared among two or more allelic products. The presence of epitopes share d between a recipient's antigen and a mismatched antigen in a donor also te nded to narrow the specificity of antibody produced. However the data also indicate differences in immunogenicity among different antigens suggesting that crossreactive group matching mould be beneficial in some but not all c ases. Finally, we present case studies to illustrate the value of ELISA in predicting humoral rejection episodes and in monitoring the efficacy of rej ection therapies. Human Immunology 62, 236-246(2001). (C) American Society for Histocomparibility and Immunogenetics, 2001. Published by Elsevier Scie nce Inc.