{"doi":"10.1111/xen.12833","title":"The impact of IdeS (imlifidase) on allo‐specific, xeno‐reactive, and protective antibodies in a sensitized rhesus macaque model","abstract":"BACKGROUND: Highly sensitized patients face many barriers to kidney transplantation, including higher rates of antibody-mediated rejection after HLA-incompatible transplant. IdeS, an endopeptidase that cleaves IgG nonspecifically, has been trialed as desensitization prior to kidney transplant, and successfully cleaves donor-specific antibody (DSA), albeit with rebound. METHODS: IdeS was generated and tested (2 mg/kg, IV) in two naïve and four allosensitized nonhuman primates (NHP). Peripheral blood samples were collected at regular intervals following IdeS administration. Total IgG, total IgM, and anti-CMV antibodies were quantified with ELISA, and donor-specific antibody (DSA) and anti-pig antibodies were evaluated using flow cytometric crossmatch. B cell populations were assessed using flow cytometry. RESULTS: IdeS successfully cleaved rhesus IgG in vitro. In allosensitized NHP, robust reduction of total, DSA, anti-pig, and anti-CMV IgG was observed within one day following IdeS administration. Rapid rebound of all IgG antibody populations was observed, with antibody levels returning to baseline around day 14 post-infusion. Total IgM level was not affected by IdeS. Interestingly, a comparable reduction in antibody populations was observed after the second dose of IdeS. However, we have not observed any significant modulation of B cell subpopulations after IdeS. CONCLUSIONS: This study evaluated efficacy of IdeS in the allosensitized NHP in IgG with various specificities, mirroring antibody kinetics in human patients. The efficacy of IdeS on preexisting anti-pig antibodies may be useful in clinical xenotransplantation. However, given the limitation of IdeS on its durability as a monotherapy, optimization of IdeS with other agents targeting the humoral response is further needed.","journal":"Xenotransplantation","year":2023,"id":346917,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9614,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1088326,"name":"Joanna Zikos","orcid":null,"position":1,"is_corresponding":false},{"id":902000,"name":"Imran J. Anwar","orcid":"0000-0002-5075-4148","position":2,"is_corresponding":false},{"id":461331,"name":"Janghoon Yoon","orcid":"0000-0001-8543-194X","position":3,"is_corresponding":false},{"id":902002,"name":"Joseph M. Ladowski","orcid":"0000-0002-6787-3725","position":4,"is_corresponding":false},{"id":286084,"name":"Annette M. Jackson","orcid":"0000-0003-2648-2944","position":5,"is_corresponding":false},{"id":399793,"name":"Koen K. A. Van Rompay","orcid":"0000-0002-7375-1337","position":6,"is_corresponding":false},{"id":527093,"name":"Diogo M. Magnani","orcid":"0000-0002-1773-2406","position":7,"is_corresponding":false},{"id":426127,"name":"Stuart J. Knechtle","orcid":"0000-0002-1625-385X","position":8,"is_corresponding":false},{"id":324233,"name":"Jean Kwun","orcid":"0000-0002-8563-5472","position":9,"is_corresponding":false},{"id":902001,"name":"Isabel DeLaura","orcid":"0000-0002-2340-0918","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:11:53.085356Z","pmid":"37864433","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}