{"doi":"10.1172/jci.insight.136678","title":"Isolevuglandins disrupt PU.1-mediated C1q expression and promote autoimmunity and hypertension in systemic lupus erythematosus","abstract":"We describe a mechanism responsible for systemic lupus erythematosus (SLE). In humans with SLE and in 2 SLE murine models, there was marked enrichment of isolevuglandin-adducted proteins (isoLG adducts) in monocytes and dendritic cells. We found that antibodies formed against isoLG adducts in both SLE-prone mice and humans with SLE. In addition, isoLG ligation of the transcription factor PU.1 at a critical DNA binding site markedly reduced transcription of all C1q subunits. Treatment of SLE-prone mice with the specific isoLG scavenger 2-hydroxybenzylamine (2-HOBA) ameliorated parameters of autoimmunity, including plasma cell expansion, circulating IgG levels, and anti-dsDNA antibody titers. 2-HOBA also lowered blood pressure, attenuated renal injury, and reduced inflammatory gene expression uniquely in C1q-expressing dendritic cells. Thus, isoLG adducts play an essential role in the genesis and maintenance of systemic autoimmunity and hypertension in SLE.","journal":"JCI Insight","year":2022,"id":248133,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"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":669289,"name":"Néstor de la Visitación","orcid":"0000-0001-7229-9601","position":1,"is_corresponding":false},{"id":886841,"name":"Jaya Krishnan","orcid":"0000-0002-9752-4219","position":2,"is_corresponding":false},{"id":298182,"name":"Wei Chen","orcid":"0000-0002-3973-340X","position":3,"is_corresponding":false},{"id":273406,"name":"Michelle J. Ormseth","orcid":"0000-0003-3734-3309","position":4,"is_corresponding":false},{"id":251751,"name":"Christoph Stein","orcid":"0000-0001-5240-6836","position":5,"is_corresponding":false},{"id":298187,"name":"Sean S. Davies","orcid":"0000-0001-9879-8062","position":6,"is_corresponding":false},{"id":886842,"name":"Venkataraman Amarnath","orcid":"0000-0001-5766-069X","position":7,"is_corresponding":false},{"id":417981,"name":"Leslie J. Crofford","orcid":"0000-0002-6347-5738","position":8,"is_corresponding":false},{"id":374828,"name":"Jonathan M. Williams","orcid":"0000-0001-8973-2950","position":9,"is_corresponding":false},{"id":298186,"name":"Shilin Zhao","orcid":"0000-0002-3921-3965","position":10,"is_corresponding":false},{"id":16586,"name":"C. Duncan Smart","orcid":"0000-0003-0391-3916","position":11,"is_corresponding":false},{"id":285541,"name":"Sergey Dikalov","orcid":"0000-0003-2976-6184","position":12,"is_corresponding":false},{"id":703872,"name":"Anna Dikalova","orcid":"0000-0002-7330-7164","position":13,"is_corresponding":false},{"id":225955,"name":"Liang Xiao","orcid":"0000-0003-0312-7149","position":14,"is_corresponding":false},{"id":265985,"name":"Justin P. Van Beusecum","orcid":"0000-0002-9265-9915","position":15,"is_corresponding":false},{"id":298183,"name":"Mingfang Ao","orcid":"0000-0002-3639-8546","position":16,"is_corresponding":false},{"id":271631,"name":"Agnes B. Fogo","orcid":"0000-0003-3698-8527","position":17,"is_corresponding":false},{"id":265986,"name":"Annet Kirabo","orcid":"0000-0001-8580-9359","position":18,"is_corresponding":false},{"id":225956,"name":"David G. Harrison","orcid":"0000-0001-9363-6451","position":19,"is_corresponding":false},{"id":265984,"name":"David M. Patrick","orcid":"0000-0002-3412-447X","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-19T00:24:09.893688Z","pmid":"35608913","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":[]}