{"doi":"10.1111/all.15868","title":"The key roles of thrombin and fibrinogen in human infant and mice atopic dermatitis models","abstract":"Atopic dermatitis (AD) affects between 15% and 24% of children in the United States1 and up to 20% of children worldwide.2 Adults with AD have increased cardiovascular risk including thromboembolic events compared to adults without AD.3 Indeed, associations between altered cutaneous and systemic clotting and atopy in adults have been observed,4-6 including a recent study which showed that adults with AD have a significant increase in cardiovascular/atherosclerosis-related proteins compared with controls.7 However, whether children with AD have altered hemostatic function remains unclear. Moreover, despite these associations in adults, the causal relationship and directionality of the association between AD and clotting has not been investigated. Herein, we investigate clotting's role in AD using the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort8 and an AD mouse model. Briefly, the MPAACH cohort is a longitudinal cohort of children with AD. Children with no history of AD or other allergic disease are recruited in parallel. The MPAACH cohort biorepository includes extensive demographic, clinical, and biomarker data including skin AD severity and transepidermal water loss (TEWL) measurements from lesional (active or historical) and never-lesional (skin never affected by AD and ≥ 10 cm away from a site of active or historical lesions), along with extensive banked longitudinal biospecimens. A full, detailed description of MPAACH and the methods used in this study8 are found within the supplementary materials. We analyzed plasma samples that had not undergone multiple freeze–thaw cycles from 99 MPAACH children. Except for age, the subset and full MPAACH cohort were similar (Table S1). Control participants without AD were recruited in parallel with the MPAACH cohort and were also included in this substudy (Table S2A). The controls were similar to the cases in terms of sex and race, but they were younger than the cases. Due to the noted age difference between the cases and controls, we restricted the analysis to children under 1 year of age including additional demographic comparisons in the <1 year of age group (Table S2B). In this age-controlled analysis, we found that children with AD had no difference in time to clot initiation (Figure 1A p = .98), but children with AD had increased peak thrombin (Figure 1B p = 8.5e-07), decreased time to peak thrombin (Figure 1C p = .04), increased rate of thrombin generation/velocity index (Figure 1D p = 8e-04), and increased total thrombin generated (Figure 1E p = .002) compared to children without AD. Insufficient children without AD that are over the age of 1 as part of MPAACH, therefore a similar analysis is not presented for this subset. Moreover, compared with controls, in the entire cohort, children with AD had shorter clot initiation phase time (p < .001, Figure S1A), higher peak thrombin (p = .0015, Figure S1B), shorter peak thrombin time (p < .001, Figure S1C), and faster thrombin generation rate (p = .003, Figure S1D). Total thrombin generation did not differ between groups (Figure S1E). Children with moderate-to-severe AD had increased total thrombin generation compared to those with mild disease (p = .043, Figure S1A). Lastly, in all children with AD, increased total plasma thrombin was associated with lesional TEWL (β = .30, p = .001, Figure S1F) and never-lesional TEWL (β = .17, p = .02, Figure S1G).These differences reflect a significant increase in the thrombin amplification phase of thrombin generation in children with AD under 1 year of age. Thrombin cleaves fibrinogen to initiate fibrin clot formation.9 Total plasma fibrinogen was inversely associated with lesional TEWL (β = −.1, p = .04). Plasma fibrinogen was not associated with other AD biomarkers (Table S3). Platelet count was not associated with lesional or never-lesional TEWL (Table S3). Lastly, two common prothrombotic variants, factor V Leiden (rs6025) and prothrombin G20210A (rs","journal":"Allergy","year":2023,"id":377483,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1141177,"name":"Peter Amezcua","orcid":null,"position":1,"is_corresponding":false},{"id":1057669,"name":"Brandy P Ruff","orcid":null,"position":2,"is_corresponding":false},{"id":476046,"name":"Jocelyn M. Biagini","orcid":null,"position":3,"is_corresponding":false},{"id":329764,"name":"John Kroner","orcid":"0000-0003-1674-9609","position":4,"is_corresponding":false},{"id":329763,"name":"Hua He","orcid":"0009-0003-2585-7684","position":5,"is_corresponding":false},{"id":550134,"name":"Eric B. Brandt","orcid":"0000-0003-0617-4100","position":6,"is_corresponding":false},{"id":32977,"name":"Lisa J. Martin","orcid":"0000-0001-8702-9946","position":7,"is_corresponding":false},{"id":364581,"name":"Joseph S. Palumbo","orcid":"0009-0005-7550-8532","position":8,"is_corresponding":false},{"id":306761,"name":"Gurjit K. Khurana Hershey","orcid":"0000-0001-6663-977X","position":9,"is_corresponding":false},{"id":329760,"name":"Michael G. Sherenian","orcid":"0000-0002-2766-729X","position":10,"is_corresponding":false},{"id":798646,"name":"Alyssa Filuta","orcid":null,"position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":null,"created_at":"2026-07-19T01:16:36.370283Z","pmid":"37646328","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":[]}