Elevated IFN-λ and IL-28R Serum Levels and Upregulated IFNL3/IFNLR1 Gene Expression in Iraqi Women with Systemic Lupus Erythematosus

Abstract

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by complex interactions of cytokines that are important mediators in the pathogenesis of SLE. However, the important roles of IFNL3 and IFNLR1 in immune responses and their correlation with gene expression levels and serum levels of SLE patients have been identified.

Aim of the study: investigated serum IFN-λ and IL-28 levels along with IFNL3/IFNLR1 gene expression in Iraqi women with SLE to determine their association with disease activity . 

Materials and Methods: The study comprised of 90 participants (60 SLE female patients aged 20-40 years, in addition to 30 healthy females (control group)) , all patients were seen at Medical City (Consultants of Arthritis, Consultant of Dermatology, Lobby of Hematology and Arthritis)/Baghdad Teaching Hospital, with data collected between 1 December 2024- 1 March 2025. The samples were diagnosed by the consultant and the immunology unit in the previously described hospitals according to their protocols . The 60 patients were divided into two groups. Group 2 (G2) consisted of 30 newly diagnosed patients, while Group 3 (G3) included 30 patients who were being treated with hydroxychloroquine 200 mg and prednisolone 5 mg twice daily. The control group consisted of 30 healthy females (G1). 5ml peripheral blood samples were withdrawn from all participants divided into two parts .4.5ml for serological study which performed by elisa assay. Where as , 0.5 ml mixed with TRIzol™ Reagent to extract mRNA and to determine the level of gene expression

Result: Newly diagnosed SLE patients (G2) showed a significantly elevated serum IFN-λ and IL-28R levels versus healthy controls (G1) and treated patients (G3) (p<0.001), with both markers exhibiting high diagnostic accuracy (AUCs 0.99 & 0.96). IFNL3 and IFNLR1 gene expression was also significantly upregulated in G2 compared to G1 and G3; IFNL3 expression itself had high diagnostic value (AUC 0.96). While IFNL3 and IFNLR1 expression correlated strongly, serum cytokine levels did not correlate with their corresponding gene expression.

Conclusion: In newly diagnosed SLE patients (G2), serum IFN-λ and IL-28R levels were much higher than those present in treated patients (G3) and controls (G1), with these serum biomarkers normalizing after appropriate treatment. Both of these showed very high diagnostic accuracy (AUC 0.99 and 0.96, respectively), and gene expression of IFNL3 and IFNLR1 was upregulated in newly diagnosed SLE patients (G2) vs both age matched treated SLE patients (G3) and controls (G1). Finally, to note, BMI had no significant effect on serum IFN-λ or IL-28R levels in any patient group (G1, G2, G3) respectively. However, significant differences (p<0.001) were found across these three patient groups for both biomarkers across each age bracket.