{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bravo-Villagra KM"],"funding":["Coecytjal. Scientific Development Fund of Jalisco to Address Social Challenges \"FODECIJAL 2023.\""],"pagination":["10011"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12562885"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(20)"],"pubmed_abstract":["Rheumatoid arthritis (RA) is characterized by chronic inflammation mediated by the JAK/STAT pathway. Variants in <i>STAT4</i> have been associated with autoimmune susceptibility, but their functional role in RA remains unclear. The aim of this study was to genetically and functionally characterize <i>STAT4</i> in RA patients with varying disease activity by analyzing two variants, mRNA expression, phosphorylated STAT4 (pSTAT4), and inflammatory cytokines (IL-12, IL-23, and IFN-γ). Sixty-three Mexican patients with RA were stratified into remission/low and moderate/high activity groups. Genotyping, <i>STAT4</i> mRNA expression, pSTAT4 quantification, cytokine profiling, and treatment analyses were conducted. Patients receiving methotrexate, hydroxychloroquine, and sulfasalazine had higher IL-12 concentrations compared with those on other regimens. In remission/low activity patients, GC/GC carriers exhibited increased IL-12, PBMC levels, and anti-CCP antibodies, while GC/TT carriers in the moderate/high activity group showed distinct ESR values. Secondary analyses revealed that TT/TT carriers with <i>STAT4</i> overexpression exhibited higher IFN-γ and IL-23 levels. IL-12 differences persisted among GC/GC carriers regardless of <i>STAT4</i> expression status. In conclusion, these exploratory findings suggest potential interactions among <i>STAT4</i> haplotypes, expression status, and treatment regimens influencing cytokine and inflammatory profiles in RA. However, due to the small subgroup sizes, the observed associations should be interpreted with caution and considered hypothesis-generating until validated in larger cohorts."],"journal":["International journal of molecular sciences"],"pubmed_title":["Genetic and Functional Characterization of STAT4 in Rheumatoid Arthritis Patients with Distinct Disease Activity."],"pmcid":["PMC12562885"],"funding_grant_id":["10627-2023"],"pubmed_authors":["Landeros-Saenz A","Hernandez-Ruiz RG","Garcia-Arellano S","Munoz-Valle JF","Banos-Hernandez CJ","Cerpa-Cruz S","Lopez-Quintero A","Bravo-Villagra KM"],"additional_accession":[]},"is_claimable":false,"name":"Genetic and Functional Characterization of STAT4 in Rheumatoid Arthritis Patients with Distinct Disease Activity.","description":"Rheumatoid arthritis (RA) is characterized by chronic inflammation mediated by the JAK/STAT pathway. Variants in <i>STAT4</i> have been associated with autoimmune susceptibility, but their functional role in RA remains unclear. The aim of this study was to genetically and functionally characterize <i>STAT4</i> in RA patients with varying disease activity by analyzing two variants, mRNA expression, phosphorylated STAT4 (pSTAT4), and inflammatory cytokines (IL-12, IL-23, and IFN-γ). Sixty-three Mexican patients with RA were stratified into remission/low and moderate/high activity groups. Genotyping, <i>STAT4</i> mRNA expression, pSTAT4 quantification, cytokine profiling, and treatment analyses were conducted. Patients receiving methotrexate, hydroxychloroquine, and sulfasalazine had higher IL-12 concentrations compared with those on other regimens. In remission/low activity patients, GC/GC carriers exhibited increased IL-12, PBMC levels, and anti-CCP antibodies, while GC/TT carriers in the moderate/high activity group showed distinct ESR values. Secondary analyses revealed that TT/TT carriers with <i>STAT4</i> overexpression exhibited higher IFN-γ and IL-23 levels. IL-12 differences persisted among GC/GC carriers regardless of <i>STAT4</i> expression status. In conclusion, these exploratory findings suggest potential interactions among <i>STAT4</i> haplotypes, expression status, and treatment regimens influencing cytokine and inflammatory profiles in RA. However, due to the small subgroup sizes, the observed associations should be interpreted with caution and considered hypothesis-generating until validated in larger cohorts.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-05-14T03:22:50.806Z","creation":"2026-05-14T03:12:36.682Z"},"accession":"S-EPMC12562885","cross_references":{"pubmed":["41155304"],"doi":["10.3390/ijms262010011"]}}