{"doi":"10.1101/2023.12.11.23299743","title":"STAT4 Phosphorylation of T-helper Cells predicts surgical outcomes in Refractory Chronic Rhinosinusitis","abstract":"Abstract Objective: Chronic rhinosinusitis (CRS) impacts an estimated 5% to 15% of people worldwide, incurring significant economic healthcare burden. There is a urgent need for the discovery of predictive biomarkers to improve treatment strategies and outcomes for CRS patients. Study design: Cohort study of CRS patients and healthy controls using blood samples. Setting: Out-patient clinics. Methods: Whole blood samples were collected for flow cytometric analysis. Mechanistic studies involved the transfection of human primary T cells and Jurkat cells. Results: Our analysis began with a 63-69 year-old female patient diagnosed with refractory CRS,. Despite undergoing multiple surgeries, she continually faced sinus infections. Whole exome sequencing pinpointed a heterozygous IL-12Rb1 mutation situated in the linker region adjacent to the cytokine binding domain. When subjected to IL-12 stimulation, the patient’s CD4 T-cells exhibited diminished STAT4 phosphorylation. However, computer modeling or T-cell lines harboring the same IL-12 receptor mutation did not corroborate the hypothesis that IL-12Rb could be responsible for the reduced phosphorylation of STAT4 by IL-12 stimulation. Upon expanding our investigation to a broader CRS patient group using the pSTAT4 assay, we discerned a subset of refractory CRS patients with abnormally low STAT4 phosphorylation. The deficiency showed improvement both in-vitro and in-vivo after exposure to Latilactobacillus sakei (aka Lactobacillus sakei ), an effect at least partially dependent on IL-12. Conclusion: In refractory CRS patients, an identified STAT4 defect correlates with poor clinical outcomes after sinus surgery, which can be therapeutically targeted by Latilactobacillus sakei treatment. Prospective double-blind placebo-controlled trials are needed to validate our findings.","journal":"medRxiv","year":2023,"id":401931,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9146,"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":259652,"name":"Oral Alpan","orcid":"0000-0001-7467-8541","position":1,"is_corresponding":false},{"id":259650,"name":"Matthew Plassmeyer","orcid":"0000-0001-8068-2125","position":2,"is_corresponding":false},{"id":318388,"name":"Lina Kozhaya","orcid":"0000-0002-1559-2278","position":3,"is_corresponding":false},{"id":1179663,"name":"Denise Loizou","orcid":null,"position":4,"is_corresponding":false},{"id":318386,"name":"Mikail Dogan","orcid":"0000-0001-8725-9151","position":5,"is_corresponding":false},{"id":1179313,"name":"Zachary Upchurch","orcid":"0009-0001-1357-5765","position":6,"is_corresponding":false},{"id":400351,"name":"Nathan P. Manes","orcid":"0000-0001-6701-3314","position":7,"is_corresponding":false},{"id":400352,"name":"Aleksandra Nita‐Lazar","orcid":"0000-0002-8523-605X","position":8,"is_corresponding":false},{"id":235097,"name":"Derya Unutmaz","orcid":"0000-0001-8898-6633","position":9,"is_corresponding":false},{"id":1179314,"name":"Søren Ulrik Sønder","orcid":"0000-0002-4697-8421","position":10,"is_corresponding":false},{"id":1179312,"name":"Michael R. Abidin","orcid":"0000-0001-5679-6667","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:20:23.920156Z","pmid":"38168423","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":[]}