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COMPLEX HLA ANTIBODY RESPONSES: EPITOPE SPECIFICITY OF HLA-A2 REACTIVE ANTIBODIES IN HIGH PRA SERA.
David Kahle, MA, Amy Zarlinga, BS, Alan Smerglia, BS, Mary Libby, BS, Daniel Cook, PhD and Edward J. Ball, PhD. Cleveland OH, USA, The Cleveland Clinic Foundation, 44195, Allogen Laboratories.

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A significant portion of patients awaiting transplant are highly sensitized to HLA as measured by PRA. The ability to find compatible donors for such patients can be facilitated by accurate determination of antibody specificities in sera from such patients.Most high PRA sera have multiple antibodies that complicate specificity analysis in traditional assays. Assays with single HLA antigen targets greatly simplifies specificity analysis. Twenty-five high PRA sera with reactivity to HLA-A2 were studied by single antigen flow bead analysis. 24/25 (96%) of the sera had reactivity in addition to HLA-A2 (2-32 "extra" reactions). Extra reactions both within (23/25, 92%) and outside of (18/25, 72%) the A2 CREG group were noted. When censored for the "extra" reaction as a self antigen, 70-80% of the sera reacted with A28 and B17. Reactions to A9 antigens were less frequent (7/16, 44%) and/or lower strength. When the proposed sequences for the epitopes shared with A2 were considered, the more frequent/stronger reactivities may be suggested to relate to exposed alpha helix positions. These results indicate that the response to an HLA molecule includes different antibody populations reactive with distinct epitopes. The frequency or strength of the different antibodies may depend on the position of the epitope on the molecule.