{"doi":"10.1101/2020.06.29.178145","title":"<i>In situ</i> humoral selection in human lupus tubulointerstitial inflammation","abstract":"ABSTRACT In human lupus nephritis, tubulointerstitial inflammation (TII) is associated with in situ expansion of B cells expressing anti-vimentin antibodies (AVAs). The mechanism by which AVAs are selected is unclear. Herein, we demonstrate that AVA somatic hypermutation and selection increase affinity for vimentin. However, enzyme-linked immunosorbent assays (ELISAs) suggested that affinity maturation might be a non-specific consequence of increasing polyreactivity. Subsequent multi-color confocal microscopy studies indicated that while TII AVAs often appeared polyreactive by ELISA, they bound selectively to vimentin fibrils in whole cells or inflamed renal tissue. Using a novel machine learning pipeline (CytoSkaler) to quantify the cellular distribution of antibody staining, we demonstrated that TII AVAs were selected for both enhanced binding and specificity in situ . These data suggest a new approach to assess and define antibody polyreactivity based on quantifying the distribution of binding to native and contextually relevant antigens.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":126996,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":512038,"name":"Yuta Asano","orcid":"0000-0002-4720-2238","position":1,"is_corresponding":false},{"id":429035,"name":"Azam Mohsin","orcid":"0000-0003-0021-3244","position":2,"is_corresponding":false},{"id":105581,"name":"Carole Henry","orcid":"0000-0002-5696-527X","position":3,"is_corresponding":false},{"id":512039,"name":"Rebecca Abraham","orcid":"0000-0001-8422-8675","position":4,"is_corresponding":false},{"id":482660,"name":"Anthony Chang","orcid":"0000-0002-6877-5510","position":5,"is_corresponding":false},{"id":512589,"name":"Christine M. Labno","orcid":null,"position":6,"is_corresponding":false},{"id":233144,"name":"Patrick C. Wilson","orcid":"0000-0002-3537-1245","position":7,"is_corresponding":false},{"id":262502,"name":"Marcus R. Clark","orcid":"0000-0003-4747-0387","position":8,"is_corresponding":false},{"id":429033,"name":"Andrew J Kinloch","orcid":"0000-0002-6827-4038","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:15:27.226519Z","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":[]}