{"doi":"10.3389/fimmu.2021.660900","title":"Measuring the Impact of Targeting FcRn-Mediated IgG Recycling on Donor-Specific Alloantibodies in a Sensitized NHP Model","abstract":"Background: In transplantation, plasmapheresis and IVIg provide the mainstay of treatment directed at reducing or removing circulating donor-specific antibody (DSA), yet both have limitations. We sought to test the efficacy of targeting the IgG recycling mechanism of the neonatal Fc receptor (FcRn) using anti-FcRn mAb therapy in a sensitized non-human primate (NHP) model, as a pharmacological means of lowering DSA. Methods: Six (6) rhesus macaque monkeys, previously sensitized by skin transplantation, received a single dose of 30mg/kg anti-RhFcRn IV, and effects on total IgG, as well as DSA IgG, were measured, in addition to IgM and protective immunity. Subsequently, 60mg/kg IV was given in the setting of kidney transplantation from skin graft donors. Kidney transplant recipients received RhATG, and tacrolimus, MMF, and steroid for maintenance immunosuppression. Results: Circulating total IgG was reduced from a baseline 100% on D0 to 32.0% (mean, SD ± 10.6) on d4 post infusion (p<0.05), while using a DSA assay. T-cell flow cross match (TFXM) was reduced to 40.6±12.5% of baseline, and B-cell FXCM to 52.2±19.3%. Circulating total IgM and DSA IgM were unaffected by treatment. Pathogen-specific antibodies (anti-gB and anti-tetanus toxin IgG) were significantly reduced for 14d post infusion. Post-transplant, circulating IgG responded to anti-FcRn mAb treatment, but DSA increased rapidly. Conclusion: Targeting the FcRn-mediated recycling of IgG is an effective means of lowering circulating donor-specific IgG in the sensitized recipient, although in the setting of organ transplantation mechanisms of rapid antibody rise post-transplant remains unaffected.","journal":"Frontiers in Immunology","year":2021,"id":179502,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":727053,"name":"Walter J. Flores","orcid":"0000-0003-0889-2958","position":1,"is_corresponding":false},{"id":461329,"name":"Robin Schmitz","orcid":"0000-0003-1286-0457","position":2,"is_corresponding":false},{"id":461330,"name":"Zachary W. Fitch","orcid":"0000-0002-1395-1513","position":3,"is_corresponding":false},{"id":461331,"name":"Janghoon Yoon","orcid":"0000-0001-8543-194X","position":4,"is_corresponding":false},{"id":727843,"name":"Yeeun Bae","orcid":null,"position":5,"is_corresponding":false},{"id":423693,"name":"Brian I. Shaw","orcid":"0000-0002-2317-6549","position":6,"is_corresponding":false},{"id":423696,"name":"Allan D. Kirk","orcid":"0000-0003-2004-5962","position":7,"is_corresponding":false},{"id":727054,"name":"Melissa J. Harnois","orcid":"0000-0002-5910-6198","position":8,"is_corresponding":false},{"id":240902,"name":"Sallie R. Permar","orcid":"0000-0003-1438-4554","position":9,"is_corresponding":false},{"id":276858,"name":"Alton B. Farris","orcid":"0000-0001-5534-7763","position":10,"is_corresponding":false},{"id":527093,"name":"Diogo M. Magnani","orcid":"0000-0002-1773-2406","position":11,"is_corresponding":false},{"id":324233,"name":"Jean Kwun","orcid":"0000-0002-8563-5472","position":12,"is_corresponding":false},{"id":426127,"name":"Stuart J. Knechtle","orcid":"0000-0002-1625-385X","position":13,"is_corresponding":false},{"id":461332,"name":"Miriam Manook","orcid":"0000-0002-6474-6122","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-18T23:47:48.974996Z","pmid":"34149698","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":[]}