{"doi":"10.1101/2023.01.25.525560","title":"Reticulocytes in donor RBC units enhance RBC alloimmunization","abstract":"Although red blood cell (RBC) transfusions save lives, some patients develop clinically-significant alloantibodies against donor blood group antigens, which then have adverse effects in multiple clinical settings. Few effective measures exist to prevent RBC alloimmunization and/or eliminate alloantibodies in sensitized patients. Donor-related factors may influence alloimmunization; thus, there is an unmet clinical need to identify which RBC units are immunogenic. Repeat volunteer blood donors and donors on iron supplements have elevated reticulocyte counts compared to healthy non-donors. Early reticulocytes retain mitochondria and other components, which may act as danger signals in immune responses. Herein, we tested whether reticulocytes in donor RBC units could enhance RBC alloimmunization. Using a murine model, we demonstrate that transfusing donor RBC units with increased reticulocyte frequencies dose-dependently increase RBC alloimmunization rates and alloantibody levels. Transfusing reticulocyte-rich RBC units was associated with increased RBC clearance from the circulation and a robust proinflammatory cytokine response. As compared to previously reported post-transfusion RBC consumption patterns, erythrophagocytosis from reticulocyte-rich units was increasingly performed by splenic B cells. These data suggest that reticulocytes in a donated RBC unit impact the quality of blood transfused, are targeted to a distinct compartment, and may be an underappreciated risk factor for RBC alloimmunization.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390908,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"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":448418,"name":"Annie Qiu","orcid":null,"position":1,"is_corresponding":false},{"id":895183,"name":"Christopher Y. Kim","orcid":"0000-0002-9215-8942","position":2,"is_corresponding":false},{"id":895185,"name":"Dominique Gordy","orcid":"0000-0001-8831-4079","position":3,"is_corresponding":false},{"id":930016,"name":"Anabel Miller","orcid":"0000-0002-2692-1655","position":4,"is_corresponding":false},{"id":859089,"name":"Maria Tredicine","orcid":"0000-0001-5909-9760","position":5,"is_corresponding":false},{"id":438368,"name":"Monika Dzieciątkowska","orcid":"0000-0002-9947-2520","position":6,"is_corresponding":false},{"id":229315,"name":"Flavia Dei Zotti","orcid":null,"position":7,"is_corresponding":false},{"id":110274,"name":"Eldad A. Hod","orcid":"0000-0002-2367-9509","position":8,"is_corresponding":false},{"id":28360,"name":"Angelo D’Alessandro","orcid":"0000-0002-2258-6490","position":9,"is_corresponding":false},{"id":110273,"name":"James C. Zimring","orcid":"0000-0002-1063-4010","position":10,"is_corresponding":false},{"id":110275,"name":"Steven L. Spitalnik","orcid":"0000-0002-8528-4561","position":11,"is_corresponding":false},{"id":110272,"name":"Krystalyn E. Hudson","orcid":"0000-0001-5663-9290","position":12,"is_corresponding":false},{"id":110266,"name":"Tiffany Thomas","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:18:42.653719Z","pmid":"36747702","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":[]}