{"doi":"10.1101/2022.03.09.22272152","title":"Afucosylation of HLA-specific IgG1 as a potential predictor of antibody pathogenicity in kidney transplantation","abstract":"Summary Antibody-mediated rejection (AMR) is the leading cause of graft failure. While donor-specific antibodies (DSA) are associated with a higher risk of AMR, not all patients with DSA develop rejection suggesting that the characteristics of alloantibodies that determine their pathogenicity remain undefined. Using human leukocyte antigen (HLA)-A2-specific antibodies as a model, we applied systems serology tools to investigate qualitative features of immunoglobulin G (IgG) alloantibodies including Fc-glycosylation patterns and Fc γ R binding properties. The levels of afucosylation of anti-A2 antibodies were elevated in all seropositive patients and were significantly higher in AMR patients, suggesting potential cytotoxicity via Fc γ RIII-mediated mechanisms. Afucosylation of both glycoengineered monoclonal and naturally glycovariant polyclonal serum IgG specific to HLA-A2 exhibited potentiated binding to, slower dissociation from, and enhanced signaling through Fc γ RIII, a receptor widely expressed on innate effector cells. Collectively, these results suggest that afucosylated DSA may be a biomarker of AMR and could contribute to its pathogenesis. Graphical Abstract. Potential influence of HLA-A2-specific IgG1 afucosylation, FcγRIIIa binding and activation on ADCC and graft rejection. Illustration created with https://BioRender.com .","journal":"medRxiv","year":2022,"id":298583,"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":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":898287,"name":"Sweta Shrestha","orcid":"0000-0002-5065-3961","position":1,"is_corresponding":false},{"id":898288,"name":"Tamás Pongrácz","orcid":"0000-0002-8089-4352","position":2,"is_corresponding":false},{"id":898289,"name":"Concetta Catalano","orcid":"0000-0001-7858-1544","position":3,"is_corresponding":false},{"id":898290,"name":"Shilpee Sharma","orcid":"0000-0003-4645-9442","position":4,"is_corresponding":false},{"id":898291,"name":"Alaín Le Moine","orcid":"0000-0001-7575-9255","position":5,"is_corresponding":false},{"id":251667,"name":"Noortje de Haan","orcid":"0000-0001-7026-6750","position":6,"is_corresponding":false},{"id":140234,"name":"Naoka Murakami","orcid":"0000-0001-8168-5811","position":7,"is_corresponding":false},{"id":56888,"name":"Leonardo V. Riella","orcid":"0000-0002-7636-3196","position":8,"is_corresponding":false},{"id":898292,"name":"Vanda Holovská","orcid":"0000-0002-2204-558X","position":9,"is_corresponding":false},{"id":53131,"name":"Manfred Wuhrer","orcid":"0000-0002-0814-4995","position":10,"is_corresponding":false},{"id":258302,"name":"Arnaud Marchant","orcid":"0000-0003-0578-0467","position":11,"is_corresponding":false},{"id":291270,"name":"Margaret E. Ackerman","orcid":"0000-0002-4253-3476","position":12,"is_corresponding":false},{"id":799265,"name":"Pranay Bharadwaj","orcid":"0000-0003-3768-3557","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-19T00:31:36.269611Z","pmid":null,"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":[]}