Expression of STAT- and T-cell-related genes in women with first-line treatment of relapsing-remitting multiple sclerosis

• Published in: Scandinavian journal of immunology 2024-11, Vol.101 (1), p.e13424
• Main Authors: Szewczak, Ludmiła, Machcińska, Maja, Kierasińska, Magdalena, Zawadzka-Więch, Urszula, Maruszewska-Cheruiyot, Marta, Majewski, Paweł, Karlińska, Anna, Rola, Rafał, Donskow-Łysoniewska, Katarzyna
• Format: Article
• Language: English
• Subjects: Adult; Crotonates; Dimethyl Fumarate - pharmacology; Dimethyl Fumarate - therapeutic use; Female; Forkhead Transcription Factors; Gene Expression Regulation - drug effects; Glatiramer Acetate - therapeutic use; Humans; Hydroxybutyrates; Inducible T-Cell Co-Stimulator Protein - genetics; Interferon-beta - therapeutic use; Middle Aged; Multiple Sclerosis, Relapsing-Remitting - blood; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - genetics; Multiple Sclerosis, Relapsing-Remitting - immunology; Nitriles - therapeutic use; Nuclear Receptor Subfamily 1, Group F, Member 3 - genetics; Phosphorylation; Signal Transduction - drug effects; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; STAT5 Transcription Factor - genetics; STAT5 Transcription Factor - metabolism; Suppressor of Cytokine Signaling 1 Protein - genetics; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Toluidines - therapeutic use; Transforming Growth Factor beta1 - blood; Transforming Growth Factor beta1 - genetics; Tumor Suppressor Proteins; Young Adult
• ISSN: 0300-9475; 1365-3083; 1365-3083
• DOI: 10.1111/sji.13424

Relapsing-remitting multiple sclerosis is associated with changes in Jak/STAT pathways in immune cells, but the influence of disease-modifying drugs on these pathways is poorly understood. The aim of this study was to evaluate the impact of first-line disease-modifying drugs used in treatment of RRMS on expression of the STAT pathway and T-cell-related genes in the blood and on serum concentrations of sgp130 and TGF-β1 in women, as well as on the level of phosphorylated STAT3 and STAT5 proteins in T cells of untreated patients and heathy controls. Expression of STAT1, STAT3, STAT5A, STAT5B, SOCS1, SOCS3, FOXP3, IKZF2, RORC and ICOS genes in the blood of untreated RRMS patients, in the blood of patients treated with interferon-β, glatiramer acetate, dimethyl fumarate or teriflunomide and in the blood of healthy controls was evaluated using droplet digital PCR. Serum concentrations of sgp130 and TGF-β1 were evaluated by ELISA. Phosphorylated STAT3 and STAT5 protein levels in T cells were evaluated by flow cytometry. STAT3 gene expression was significantly higher in untreated patients than in healthy control, but the level of phosphorylated STAT3 in T cells was significantly lower. Patients treated with interferon-β or dimethyl fumarate had significantly lower STAT3 gene expression. Patients treated with teriflunomide had higher STAT1 gene expression, than untreated patients. Patients treated with dimethyl fumarate also had significantly lower RORC gene expression than untreated patients. The study shows the impact of drugs used in first-line treatment of relapsing-remitting multiple sclerosis on expression of STAT and T-cell-related genes.