Determining what happens to the genes FOXP3, RORγt, SOCS1, STAT3, STAT5, and SMAD3 in patients with ankylosing spondylitis who received anti-TNF therapy

Abstract

Abstract Background/Objective: Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease that affects the axial skeleton, causing characteristic inflammatory back pain. We aim to examine the genes FOXP3, RORγt, SOCS1, STAT3, STAT5, and SMAD3 in patients with ankylosing spondylitis who receive anti-TNF therapy to understand the progression of the disease in a clinically improved or failed response to anti-TNF treatment. Method: A prospective case-control study was conducted at Basrah Teaching Hospital in southern Iraq. Eighty-one AS patients were divided into two groups: 67 were treated with anti-TNF therapy; 14 were newly diagnosed patients as positive controls, and 65 were healthy individuals. Disease activity was assessed using the AS Bath Disease Activity Index (BASDAI). Conventional radiography and MRI are used to measure the severity of the disease. Blood samples were homogenized, and mRNA was isolated using a total RNA extraction kit. Reverse transcription (RT) was performed. The gene expression of RORγt, FOXP3, SOCS1, SAMD1, SMAD3, STAT3, and STAT5 was detected by implementing a real-timePCR system. Result: There was significant downregulation of the FOXP3 gene in anti-TNF-treated AS patients and biologically naïve AS patients compared to healthy control people, which may be due to how the disease affects the expression and activity of the FOXP3 gene, which does not change with the type of therapy (P = 0.001). RORγt expression was higher in both established and newly diagnosed AS patients (p 0.001) than in healthy controls. The SOCS1 gene was expressed at a low level in patients with AS and positive control patients compared to the SOCS1 gene in healthy control individuals (p 0.780). STAT3 expression was lower in established and biologically naïve AS patients than in healthy subjects. Simultaneously, biologically normal AS patients had higher levels of STAT5 in this group. SMAD3 was underexpressed in established and biologically naïve AS patients compared to healthy subjects. Conclusion: The progression of AS in patients treated with anti-TNF therapy is linked to a secondary change in the expression of the genes FOXP3, RORγt, SOCS1, STAT3, STAT5, and SMAD3 that leads to the induction of exTh17cells.