Drug screening and identification of key candidate genes and pathways of rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA), which normally manifests as a multi-joint inflammatory reaction, is a common immunological disease in clinical practice. However, the pathogenesis of RA has not yet been fully elucidated. Rituximab (RTX) is an effective drug in the treatment of RA, however its therapeutic efficacy and mechanism of action require further investigation. Thus, the present study aimed to screen the candidate key regulatory genes and explain the potential mechanisms of RA . Gene chips of RA and normal joint tissues were analyzed and, gene chips of RTX before and after treatment were investigated. In the present study, strong evidence supporting the pathogenesis of RA and mechanism of action of RTX were also revealed. Differentially expressed genes (DE Gs) were analyzed using the limma package of RStudio software. A total of 1,150 DE Gs were detected in RA compared with normal joint tissues. The upregulated genes were enriched in 'interleukin-12 production', 'I- κB kinase/NF-κB signaling', 'regulation of cytokine production involved in immune response' and 'cytokine metabolic process'. Functional enrichment analysis showed that RTX was primarily involved in the inhibition of 'adaptive immune response', κB cell activation involved in immune response' and 'immune effector process'. Subsequently, leukocyte immunoglobulin-like receptor subfamily B member 1 (LILR B1), a hub gene with high connectivity degree, was selected, and traditional Chinese medicine libraries were molecularly screened according to the structure of the LILR B1 protein. The results indicated that kaempferol 3-O- β-D- glucosyl-(1→2)-β-D- glucoside exhibited the highest docking score. In the present study, the DE Gs and their biological functions in RA and the pharmacological mechanism of RTX action were determined. Taken together, the results suggested that LILR B1 may be used as a molecular target for RA treatment, and kaempferol 3-O- β-D- -glucosyl-(1→2)-β-D- glucoside may inhibit the pathological process of RA .