The current study aims to test four aspects associated with the pathogenesis of lupus erythematosus in two groups of Iraqi patients with and without lupus nephritis. The first aspect included evaluation of some blood components and indicators of kidney function, as well as evaluation of some immunological factors and serum levels of IL-23 cytokine and its receptor IL-23R using ELISA technique. As for the third aspect, it included determining the expression level of miRNA-21-5P in plasma using quantitative polymerase chain reaction (RT-qPCR) technique. While the fourth aspect included genotyping and testing of cytokinetic polymorphisms of IL-23 (rs11171806) and IL-23R (rs11209026 and rs10489629) using conventional polymerase chain reaction and Sanger method. The study concluded that immune factors and renal function indicators continued to deteriorate, indicating that the currently used treatments are not effective in affecting these factors or inhibiting the IL-23 pathway, which is largely implicated in the complex events of the disease. The study showed an abnormal expression of miRNA-21-5P between the two groups of patients as well as its negative association with sIL-23 level and positive association with sIL-23R level. The results of the study shed light on the molecular pathway in which the rs11209026 variant affects the production of the soluble form of IL-23R as well as assessment of sIL-23/sIL-23R ratio. The study concluded that miRNA-21-5P could be a new diagnostic tool to predict kidney injury as well as a protective factor against the development of lupus renal disease. The results of the study confirmed that the adoption of gene therapy based on soluble receptors represents an innovative and promising solution to reduce the complex events of the disease and improve the life expectancy of patients.