{"doi":"10.1161/circheartfailure.124.011729","title":"IL1RAP Blockade With a Monoclonal Antibody Reduces Cardiac Inflammation and Preserves Heart Function in Viral and Autoimmune Myocarditis","abstract":"BACKGROUND: Currently, there are no therapies targeting specific pathogenic pathways in myocarditis. IL (interleukin)-1 blockade has shown promise in preclinical studies and case reports. We hypothesized that blockade of IL1RAP (IL-1 receptor accessory protein), a shared subunit of the IL-1, IL-33, and IL-36 receptors, could be more efficient than IL-1 blockade alone. METHODS: We induced coxsackievirus B3 (CVB3)–mediated or experimental autoimmune myocarditis (EAM) in BALB/c mice, followed by treatment with an Fc (fragment crystallizable)-modified mIgG2a mouse anti-mouse IL1RAP monoclonal antibody (mCAN10). Myocarditis severity and immune infiltration were assessed by histology and flow cytometry. Cardiac function was measured by echocardiography. We used spatial transcriptomics (Visium 10× Genomics) to compare the gene expression landscape in the hearts of mCAN10-treated versus control mice. RESULTS: IL1RAP blockade reduced CVB3 and EAM severity. In EAM, the treatment prevented deterioration of cardiac function, measured on day 42 post-disease induction (left ventricular ejection fraction: 56.5% versus 51.0% in isotype controls [ P =0.002] and versus 51.4% in mice treated with anti-IL-1β antibodies alone [ P =0.003]; n=10–11 mice per group). In the CVB3 model, mCAN10 did not impede viral clearance from the heart and significantly lowered the numbers of CD4 + (cluster of differentiation 4) T cells ( P =0.025), inflammatory Ly6C + CCR2 + (lymphocyte antigen 6 complex, locus C/C-C motif chemokine receptor 2) monocytes ( P =0.038), neutrophils ( P =0.001) and eosinophils ( P <0.001) infiltrating the myocardium. The spatial transcriptomic analysis revealed reduced canonical IL-1 signaling and chemokine expression in cardiac immune foci in CVB3-infected mice treated with IL1RAP blockade. CONCLUSIONS: Blocking IL1RAP reduces acute CVB3 myocarditis and EAM severity and preserves cardiac function in EAM. We conclude that IL1RAP blockade is a potential therapeutic strategy in viral and autoimmune myocarditis.","journal":"Circulation Heart Failure","year":2024,"id":428409,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9629,"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":1229610,"name":"Gabriel Jakobsson","orcid":"0000-0001-5071-9505","position":1,"is_corresponding":false},{"id":1081639,"name":"Abdel Daoud","orcid":"0009-0004-6661-5670","position":2,"is_corresponding":false},{"id":381834,"name":"David S. Elias","orcid":"0000-0002-4363-3057","position":3,"is_corresponding":false},{"id":465559,"name":"Monica V. Talor","orcid":"0000-0002-8275-5698","position":4,"is_corresponding":false},{"id":500587,"name":"Sara Rattik","orcid":"0000-0002-5172-6456","position":5,"is_corresponding":false},{"id":1226401,"name":"Caitríona Grönberg","orcid":"0009-0000-3776-5566","position":6,"is_corresponding":false},{"id":1116423,"name":"Hannah Kalinoski","orcid":"0000-0002-2732-0077","position":7,"is_corresponding":false},{"id":1226400,"name":"Elin Jaensson Gyllenbäck","orcid":"0000-0002-1334-8642","position":8,"is_corresponding":false},{"id":492566,"name":"Nadan Wang","orcid":"0000-0002-1682-080X","position":9,"is_corresponding":false},{"id":715331,"name":"David Liberg","orcid":"0009-0009-0645-746X","position":10,"is_corresponding":false},{"id":1155249,"name":"Alexandru Șchiopu","orcid":"0000-0002-7587-5050","position":11,"is_corresponding":false},{"id":465563,"name":"Daniela Čiháková","orcid":"0000-0002-8713-2860","position":12,"is_corresponding":false},{"id":255406,"name":"Diego Lema","orcid":"0000-0001-7910-1127","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:58:57.592578Z","pmid":"39513273","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":[]}