{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:38:59Z","timestamp":1763375939304,"version":"3.45.0"},"reference-count":43,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Laquinimod (LAQ) and interferon-\u03b21a (IFN-\u03b21a, Rebif) are immunomodulatory therapies for relapsing\u2013remitting multiple sclerosis (RRMS) that may also influence vascular and hemostatic pathways. This study investigated transcriptional regulation of coagulation- and fibrinolysis-related genes in peripheral blood mononuclear cells (PBMCs) from LAQ- and IFN-\u03b21a\u2013treated RRMS patients. In the LAQ cohort, within-subject paired analysis revealed significant downregulation of procoagulant and antifibrinolytic transcripts, including F2, F10, SERPINE1 (PAI-1), and TFPI, after six months of treatment (FDR &lt; 0.01, |fold change| \u2265 1.5). These findings suggest that LAQ exerts an anticoagulant and antifibrinolytic transcriptional effect, potentially mediated through aryl hydrocarbon receptor (AhR) signaling. Western blot analysis confirmed decreased PAI-1 protein expression. In contrast, IFN-\u03b21a treatment induced a distinct transcriptional pattern. Genes associated with fibrinolysis and endothelial stabilization (THBD, ANXA2, SERPINA1) were upregulated, while procoagulant mediators (F2R, F13A1, PROS1) were downregulated. Correlation analysis demonstrated significant relationships between interferon-inducible genes and coagulation-related transcripts, suggesting coordinated regulation between type I interferon signaling and vascular pathways. Collectively, these results indicate that LAQ and IFN-\u03b21a exert opposing yet convergent influences on coagulation and fibrinolytic networks in immune cells. Both therapies modulate transcriptional regulators of vascular homeostasis, revealing a potential molecular interface between immune modulation and hemostatic balance in RRMS. These findings are exploratory and hypothesis-generating, warranting further functional and clinical validation.<\/jats:p>","DOI":"10.3390\/ijms262211106","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:24:58Z","timestamp":1763375098000},"page":"11106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beta Interferon 1a and Laquinimod Differentially Affect Coagulation-Related Gene Expression in Multiple Sclerosis Patients: Implications for Clinical Efficacy and Side Effects"],"prefix":"10.3390","volume":"26","author":[{"given":"Michael","family":"Gurevich","sequence":"first","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan 52621, Israel"},{"name":"Department of Neurology, Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4980-191X","authenticated-orcid":false,"given":"Rina","family":"Zilkha-Falb","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan 52621, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joab","family":"Chapman","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan 52621, Israel"},{"name":"Department of Neurology, Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tali","family":"Drori","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan 52621, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jneuroim.2012.06.005","article-title":"Oral treatment with laquinimod augments regulatory T-cells and brain-derived neurotrophic factor expression and reduces injury in the CNS of mice with experimental autoimmune encephalomyelitis","volume":"251","author":"Aharoni","year":"2012","journal-title":"J. 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