University Publications

Graduate Studies Journal - Volume 18 - Issue (52573) - Role of IL-9 in the Pathogenesis of Systemic Lupus Erythematosus

Abstract

Background: Systemic lupus erythematosus (SLE) is a complex and polyetiological autoimmune disease with chronic relapsing-remitting course and variable clinical and immunopathological manifestations leading to a spectrum ranging from mild mucocutaneous to devastating, life-threatening multiorgan illness. A cytokine called IL9 controls the activity of different hematopoietic cells. This cytokine promotes cell growth and staves off apoptosis. It works by activating numerous signal transducer and activator (STAT) proteins, which link this cytokine to several biological processes through the interleukin 9 receptor (IL9R). Asthma has been linked to the gene that produces this cytokine. Objectives: To assess the role of IL-9 in the pathogenesis of Systemic Lupus Erythematosus by measuring the serum levels of IL9 and the fold change of the expression of IL9 mRNA, and related biomarkers in patients with SLE and healthy controls. Materials and Methods: In a cross-sectional study conducted at the Rheumatology Clinic, Military Hospital and the Institute of Endemic Diseases, University of Khartoum, Sudan. Ethical Approval was obtained from The Central Institutional Review Board, Al Neelain University. Following informed consents, 59 patients of both sexes with SLE and 26 healthy controls were included in the study. From each patient and a control 5ml venous blood were obtained. Serum was separated and stored at -80 ͦ c and later used for measurement of IL9, IL10, IFN-γ using Sandwich ELISA, C Reactive Protein, complement 4, complement 3 were measured using turbidimetric immunoassay. PBMCs were used for the expression of IL9 mRNA. Demographic, clinical and laboratory data were collected in special case report forms. Data were analyzed using SPSS v28.0.1. Results: Anaemia was the most frequent finding (n=34; 57%) in patients whereas arthritis is least (n=12; 20.3%). C3 and C4 were significantly decreased in SLE patients compared to health individuals (C3 in patients was 52.04±21.8, C3 in controls was 98.7±28.5; C4 in patients was 7.1±2.7, C4 in controls was 19.3±8.9 (p=0.0001). The mean levels of CRP measured in the serum of patients with SLE, and controls were (31.1±27.5 mg/l) than that of the controls (5.8±6.7 mg/l) respectively. There is a statistically significant difference between the patients and the controls, (p=0.01). The mean levels of IL9 in patients was found to be higher (162.7±290.9 pg/ml) compared with the controls (55.2±51.3 pg/ml), (p=0.01). Mean serum IL-10 level was significantly increased in patients compared with the controls (P<0.01) whereas, serum IFN-γ mean level was decreased in patients compared with the controls (P<0.28). The fold change of IL 9 mRNA expression in patients and control group were 21.7 and 4.4 respectively. This is interpreted as the expression of IL-9 mRNA was increased by more than fourfold (4.9) due to SLE. This indicates that the outcome of the IL9 level is upregulated at different levels in patients with SLE. Conclusion: IL9 as a protein is high in patients with SLE together with IL10 which indicates a Th2 response. Likewise, the expression of IL9 mRNA is upregulated in patients explaining the higher level in the serum. In contradistinction, IFN-γ is low in patients which indicates skewed immune response to Th2. Therefore, IL9 is central in the immune response in SLE both at the gene and the protein levels.