Jiaqian Wang,1 Yuan Xue,2 Liang Zhou3 

1Department of Orthopaedic, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Orthopaedic, Wuxi Ninth People’s Hospital of Soochow University, Wuxi, 214000, People’s Republic of China; 3Department of Orthopaedic, Lianshui County People’s Hospital, Huai‘an, People’s Republic of China

Correspondence: Jiaqian Wang, Email 1580443814@qq.com

Background: Rheumatoid arthritis (RA) is a chronic systemic immune disease characterized by joint synovitis, but there are differences in clinical manifestations and serum test results among different patients.
Methods: This is a bioinformatics study. We first obtained the gene expression profile of RA and normal synovium from the database, and screened the differentially expressed immune related genes for enrichment analysis. Subsequently, we classified RA into three subtypes by unsupervised clustering of serum gene expression profiles based on immune enrichment scores. Then, the enrichment and clinical characteristics of different subtypes were analyzed. Finally, according to the infiltration of different subtypes of immune cells, diagnostic markers were screened and verified by qRT-PCR.
Results: C1 subtype is related to the increase of neutrophils, C-reactive protein and erythrocyte sedimentation rate, and joint pain is more significant in patients. C2 subtype is related to the expression of CD8+T cells and Tregs, and patients have mild joint pain symptoms. The RF value of C3 subtype is higher, and the expression of various immune cells is increased. CD4 T cells, NK cells activated, macrophages M1 and neutrophils are immune cells significantly infiltrated in synovium and serum of RA patients. IFNGR1, TRAC, IFITM1 can be used as diagnostic markers of different subtypes.
Conclusion: In this study, RA patients were divided into different immune molecular subtypes based on gene expression profile, and immune diagnostic markers were screened, which provided a new idea for the diagnosis and treatment of RA.

Keywords: rheumatoid arthritis, molecular subtype, immune cells, immunodiagnostic markers