59-OR

Abstract

Aim While it is generally accepted that HLA antibodies (Abs) represent significant risk factors for transplant rejection and graft failure, it has become apparent that Abs are specific for epitopes (Eps), not HLA antigens. A distinction between HLA Eps and antigens is important not only for the determination of mismatch acceptability for sensitized patients but also for a better understanding of the Ab response to an HLA mismatch. Numerous publications describe Ep-specific Abs, but there is no standardized information about the repertoire of clinically relevant HLA Eps. Under auspices of the 16 th IHIW we developed a website-based registry of Ab-verified HLA Eps. Ep notations are based on HLA molecular modeling of amino acid residues in polymorphic sequence positions. Methods Informative Ep-specific Abs were induced by transplant, transfusion or pregnancy, or were monoclonal Abs or eluates of sera absorbed with single HLA alleles. Ab reactivity was determined in binding assays with single allele panels. Ab producer/immunizer HLA types enhanced the characterization of specific Eps. The registry also includes Eps described in original research publications. Based on the extent of Ab reactivity information, we assigned Ep status as confirmed (well-documented) or provisional (more data needed). At present, the registry has 77 HLA-ABC, 52 DRB1/3/4/5, 17 DQAB, 8 DPAB and 6 MICA Ab-verified Eps. Laboratories worldwide continue to submit data about previously unreported Ab-specific Eps. Results For each Ep, the website shows its amino acid composition and HLA alleles that share the Ep. A link shows Ab reactivity, sensitization information and references. Another link shows molecular modeling of corresponding structural Eps and polymorphic residue information for Ep-carrying alleles. The website will also have a link to Ep frequency information in different populations. Conclusions The HLA Epitope Registry website will become a valuable resource for researchers investigating Ab responses to HLA mismatches.