{"doi":"10.1172/jci151520","title":"The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children","abstract":"Multisystem inflammatory syndrome in children (MIS-C) manifests as a severe and uncontrolled inflammatory response with multiorgan involvement, occurring weeks after SARS-CoV-2 infection. Here, we utilized proteomics, RNA sequencing, autoantibody arrays, and B cell receptor (BCR) repertoire analysis to characterize MIS-C immunopathogenesis and identify factors contributing to severe manifestations and intensive care unit admission. Inflammation markers, humoral immune responses, neutrophil activation, and complement and coagulation pathways were highly enriched in MIS-C patient serum, with a more hyperinflammatory profile in severe than in mild MIS-C cases. We identified a strong autoimmune signature in MIS-C, with autoantibodies targeted to both ubiquitously expressed and tissue-specific antigens, suggesting autoantigen release and excessive antigenic drive may result from systemic tissue damage. We further identified a cluster of patients with enhanced neutrophil responses as well as high anti-Spike IgG and autoantibody titers. BCR sequencing of these patients identified a strong imprint of antigenic drive with substantial BCR sequence connectivity and usage of autoimmunity-associated immunoglobulin heavy chain variable region (IGHV) genes. This cluster was linked to a TRBV11-2 expanded T cell receptor (TCR) repertoire, consistent with previous studies indicating a superantigen-driven pathogenic process. Overall, we identify a combination of pathogenic pathways that culminate in MIS-C and may inform treatment.","journal":"Journal of Clinical Investigation","year":2021,"id":147442,"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":159,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"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":582309,"name":"Aleksandra Binek","orcid":"0000-0001-5764-7137","position":1,"is_corresponding":false},{"id":231572,"name":"Lisa Paschold","orcid":"0000-0003-0020-1315","position":2,"is_corresponding":false},{"id":231571,"name":"Magali Noval Rivas","orcid":"0000-0001-5570-8928","position":3,"is_corresponding":false},{"id":627475,"name":"Angela McArdle","orcid":"0000-0002-4006-8320","position":4,"is_corresponding":false},{"id":243044,"name":"Lael M. Yonker","orcid":"0000-0003-1711-8227","position":5,"is_corresponding":false},{"id":106757,"name":"Galit Alter","orcid":"0000-0002-7680-9215","position":6,"is_corresponding":false},{"id":556543,"name":"Harsha Chandnani","orcid":null,"position":7,"is_corresponding":false},{"id":556544,"name":"Merrick Lopez","orcid":null,"position":8,"is_corresponding":false},{"id":227641,"name":"Alessio Fasano","orcid":"0000-0002-2134-0261","position":9,"is_corresponding":false},{"id":112291,"name":"Jennifer E. Van Eyk","orcid":"0000-0001-9050-148X","position":10,"is_corresponding":false},{"id":231574,"name":"Mascha Binder","orcid":"0000-0003-0663-3004","position":11,"is_corresponding":false},{"id":231575,"name":"Moshe Arditi","orcid":"0000-0001-9042-2909","position":12,"is_corresponding":false},{"id":231570,"name":"Rebecca A. Porritt","orcid":"0000-0002-0973-5092","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-18T23:42:35.448762Z","pmid":"34437303","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":[]}