CHALLENGES AND OPPORTUNITIES IN BRINGING NON-HLA ANTIBODY TESTING TO THE LAB FOR POST-TRANSPLANT MONITORING

Mary Carmelle Philogene^1*Inna Tchoukina¹Idoia Gimferrer²

• ¹Virginia Commonwealth University, Richmond, United States
• ²Bloodworks Northwest Research Institute, Seattle, Washington, United States

Evidence for the contribu�on of non-HLA an�bodies on long-term allogra� outcome was suggested in early studies by Paul Terasaki and colleagues who showed worse 10-year allogra� outcome in HLA iden�cal kidney transplant recipients with a posi�ve panel reac�ve an�body (PRA) as determined by the micro cytotoxicity assay, in which cells express other targets beside HLA. More recent reports have shown worse gra� outcome when an�bodies against non-HLA an�gens were detected with HLA-donor specific an�bodies (HLA-DSA), and even suggest that non-HLA an�bodies may serve as precursor to development of HLA an�bodies. Unfortunately, the recent studies lack reproducibility, which then leads to skep�cism as to the relevance of non-HLA an�body in transplanta�on outcome. Consequently, rou�ne tes�ng for non-HLA an�body along with monitoring of HLA-DSA as part of a post-transplant immune surveillance protocol is not standard prac�ce. The Sensi�za�on in Transplanta�on: Assessment of Risk (STAR) workgroup summarized the current literature on this topic, ci�ng differences in cohort characteris�cs, variability in study design, selec�on of sample and �mepoints for tes�ng and variability in the assays used to detect non-HLA an�bodies, as reasons that impact the accurate assessment on the relevance of non-HLA an�bodies. However, correla�on between test results and outcome can only be determined if the assay in ques�on is detec�ng the correct analyte. Therefore, here we will make the case for a plan that requires a systema�c valida�on of high-throughput bead-based assays, to include appropriate sequence selec�on for non-HLA an�genic targets and quality control metrics as a first step to solving this puzzle.