{"doi":"10.1172/jci176466","title":"Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria","abstract":"BACKGROUNDFeatures of consumptive coagulopathy and thromboinflammation are prominent in cerebral malaria (CM). We hypothesized that thrombogenic autoantibodies contribute to a procoagulant state in CM.METHODSPlasma from children with uncomplicated malaria (UM) (n = 124) and CM (n = 136) was analyzed by ELISA for a panel of 8 autoantibodies including anti-platelet factor 4/polyanion (anti-PF4/P), anti-phospholipid, anti-phosphatidylserine, anti-myeloperoxidase, anti-proteinase 3, anti-dsDNA, anti-β-2-glycoprotein I, and anti-cardiolipin. Plasma samples from individuals with nonmalarial coma (NMC) (n = 49) and healthy controls (HCs) (n = 56) were assayed for comparison. Associations with clinical and immune biomarkers were determined using univariate and logistic regression analyses.RESULTSMedian anti-PF4/P and anti-PS IgG levels were elevated in individuals with malaria infection relative to levels in HCs (P < 0.001) and patients with NMC (PF4/P: P < 0.001). Anti-PF4/P IgG levels were elevated in children with CM (median = 0.27, IQR: 0.19-0.41) compared with those with UM (median = 0.19, IQR: 0.14-0.22, P < 0.0001). Anti-PS IgG levels did not differ between patients with UM and those with CM (P = 0.39). When patients with CM were stratified by malaria retinopathy (Ret) status, the levels of anti-PF4/P IgG correlated negatively with the peripheral platelet count in patients with Ret+ CM (Spearman's rho [Rs] = 0.201, P = 0.04) and associated positively with mortality (OR = 15.2, 95% CI: 1.02-275, P = 0.048). Plasma from patients with CM induced greater platelet activation in an ex vivo assay relative to plasma from patients with UM (P = 0.02), and the observed platelet activation was associated with anti-PF4/P IgG levels (Rs= 0.293, P = 0.035).CONCLUSIONSThrombosis mediated by elevated anti-PF4/P autoantibodies may be one mechanism contributing to the clinical complications of CM.","journal":"Journal of Clinical Investigation","year":2024,"id":457513,"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":0.9693,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":407920,"name":"Anne Kessler","orcid":null,"position":1,"is_corresponding":false},{"id":406371,"name":"Visopo Harawa","orcid":"0000-0003-0682-1689","position":2,"is_corresponding":false},{"id":406373,"name":"Ajisa Ahmadu","orcid":"0000-0001-8248-7841","position":3,"is_corresponding":false},{"id":760786,"name":"Thomas E. Keller","orcid":"0000-0002-9198-5073","position":4,"is_corresponding":false},{"id":406374,"name":"Stephen Ray","orcid":"0000-0001-5818-1228","position":5,"is_corresponding":false},{"id":75970,"name":"Terrie E. Taylor","orcid":"0000-0001-7416-3986","position":6,"is_corresponding":false},{"id":406377,"name":"Stephen J. Rogerson","orcid":"0000-0003-4287-1982","position":7,"is_corresponding":false},{"id":406376,"name":"Wilson L. Mandala","orcid":"0000-0001-9386-9239","position":8,"is_corresponding":false},{"id":554041,"name":"Morayma Reyes Gil","orcid":"0000-0002-8011-4707","position":9,"is_corresponding":false},{"id":75973,"name":"Karl B. Seydel","orcid":"0000-0001-9859-9549","position":10,"is_corresponding":false},{"id":406378,"name":"Kami Kim","orcid":"0000-0003-3384-152X","position":11,"is_corresponding":false},{"id":1283091,"name":"Iset Medina Vera","orcid":"0000-0002-3373-9683","position":0,"is_corresponding":true}],"reference_count":122,"raw_metadata":null,"created_at":"2026-07-19T02:03:41.744499Z","pmid":"38652559","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":[]}