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Individuals with broadly reactive HLA antibodies due to prior exposure to foreign HLA are potential candidates for a clinical xenotransplant trial. It remains controversial if allosensitisation results in the development of cross\u2010reactive antibodies against SLA. This may require increased histocompatibility scrutiny for highly sensitised individuals prior to enrollment in a clinical trial. Serum samples were obtained from non\u2010human primates sensitised via serial skin transplantation from maximally MHC\u2010mismatched donor, as reported. Sera from pre\u2010 and post\u2010allosensitisation timepoints were assessed in a flow crossmatch (FXM) for IgM and IgG binding to pig splenocytes with or without red blood cell adsorption. Xenoreactive antibodies were eluted from pig splenocytes and screened on a single antigen HLA bead assay. A MHC Matchmaker algorithm was developed to predict potential conserved amino acid motifs among the pig, NHP, and human. Our sensitised NHP model was used to demonstrate that allosensitisation does not result in an appreciable difference in xenoreactive antibody binding in a cell\u2010based FXM. However, antibody elution and screening on single antigen HLA beads suggest the existence of potential cross\u2010reactive antibodies against SLA. The cross\u2010reactive IgG after allosensitisation were predicted by comparing the recipient Mamu alleles against its previous allograft donor Mamu alleles and the donor pig SLA alleles. Our study suggests that allosensitisation could elevate cross\u2010reactive antibodies, but a more sensitive assay than a cell\u2010based FXM is required to detect them. The MHC Matchmaker algorithm was developed as a potential tool to help determine amino acid motif conservation and reactivity pattern.<\/jats:p>","DOI":"10.1111\/tan.15599","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T05:37:15Z","timestamp":1721713035000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Allosensitisation in\n                    <scp>NHP<\/scp>\n                    results in cross\u2010reactive anti\u2010\n                    <scp>SLA<\/scp>\n                    antibodies not detected by a lymphocyte\u2010based flow cytometry crossmatch"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6787-3725","authenticated-orcid":false,"given":"Joseph M.","family":"Ladowski","sequence":"first","affiliation":[{"name":"Duke Transplant Center, Department of Surgery Duke University School of Medicine  Durham North Carolina 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