{"doi":"10.1111/xen.70045","title":"Desensitization With Proteasome Inhibition and Costimulation Blockade Modulates the Xenoreactive Humoral Response in Nonhuman Primate Xenotransplantation","abstract":"INTRODUCTION: \"Delayed\" antibody-mediated xenograft rejection is one of the most important obstacles to clinical application of pig organ xenografts. The aim of this study was to assess the impact of a structured desensitization regimen including proteasome inhibition and next-generation costimulation blockade on xenoreactive antibodies. METHODS: ), anti-CD154 (20 mg/kg) every other week, and CD4 and CD20 lymphocyte cell depletion. Bone marrow was acquired to assess plasma cell depletion in response to proteasome inhibition. A flow cytometry-based xenoreactive crossmatch assay was performed to assess levels of circulating xenoreactive antibodies. RESULTS: The desensitization regimen resulted in a >50% depletion of CD38+CD27+ bone marrow plasma cells; these changes were progressive over the duration of the desensitization treatment period. The desensitization strategy and plasma cell depletion resulted in a progressive reduction in anti-pig IgG antibodies. Following xenotransplantation, both desensitized recipients demonstrated superior graft survival to a highly xenoreactive recipient (MST 30 days vs. 6 days), but neither desensitized recipient experienced prolonged graft survival. CONCLUSIONS: A structured desensitization regimen including proteasome inhibition and costimulation blockade results in plasma cell depletion and resultant reduction in circulating xenoreactive anti-pig IgG antibodies, with a modest improvement in xenograft survival. This desensitization regimen has promise for pig-to-NHP xenotransplant models.","journal":"Xenotransplantation","year":2025,"id":521019,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9667,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1390883,"name":"Abraham J. Matar","orcid":"0000-0001-7351-7674","position":1,"is_corresponding":false},{"id":301369,"name":"Jakob Habib","orcid":"0000-0002-8720-8757","position":2,"is_corresponding":false},{"id":635388,"name":"David A. Faber","orcid":null,"position":3,"is_corresponding":false},{"id":634201,"name":"Cynthia Breeden","orcid":"0000-0001-8716-4435","position":4,"is_corresponding":false},{"id":276858,"name":"Alton B. Farris","orcid":"0000-0001-5534-7763","position":5,"is_corresponding":false},{"id":634205,"name":"A. Joseph Tector","orcid":"0000-0002-9865-8382","position":6,"is_corresponding":false},{"id":369210,"name":"Andrew Adams","orcid":"0000-0001-8925-9956","position":7,"is_corresponding":false},{"id":634200,"name":"Brendan P. Lovasik","orcid":"0000-0002-3770-2079","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T02:49:32.958846Z","pmid":"40259710","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":[]}