Investigating the Association of Gene Expression of IL-37 Isoforms a and b and Serum IL-37 with Rheumatoid Arthritis Activity and Severity

Abstract Background: New rheumatoid arthritis (RA) biomarkers, such as serum interleukin-37, may aid in the identification and management as well as improved monitoring of disease severity, activity, and effectiveness of the therapy. Objectives: This study aims to assess the association between gene expressions of interleukin (IL)-37 isoform-a and isoform-b and serum IL-37 levels with the severity and activity of RA. Materials and Methods: This is a case–control study of 140 participants. The samples were collected using fresh blood and serum samples. The sample consisted of 64 females and six males in both the patient and control groups. The serum IL-37 level was measured using enzyme-linked immunosorbent assay. Immune markers such as anti-cyclic citrullinated peptide (anti-CCP), erythrocyte sedimentation rate (ESR), rheumatoid factor, and C-reactive protein (CRP) were also measured. Gene expression for IL-37 isoforms was measured by real-time quantitative polymerase chain reaction (PCR). DAS-28-ESR, DAS-28-CRP, and CDAI were used to calculate the activity of RA as well as the severity of disease. Results: The serum levels of IL-37 were significantly higher in patients than in controls. Activity parameters, as stated by DAS-28 ESR, DAS-28 CRP, CDAI, and SDAI, showed a positive correlation with serum levels of IL-37. The levels of IL-37 correlated significantly with the treatment response. There was a significant correlation between IL-37 levels and ESR, CRP, and anti-CCP levels. IL-37 isoform-a mRNA expression, measured by RT-qPCR, was upregulated in patients with severity. In addition, the isoform-b gene expression was downregulated, in contrast to control groups for both genes, who showed normal expression for these genes. Conclusion: Serum IL-37 and IL-37 isoform-a are promising biomarkers for the diagnosis of RA, assessing disease activity and severity in patients with RA, and offering possible future therapeutic applications for RA patients, while IL-37 isoform-b is considered a weak biomarker for diagnosing RA.