CD27 Neutralization Attenuates Rheumatoid Arthritis by Suppressing

Area of Science:

• Immunology
• Rheumatology
• Biomarker Discovery

Background:

• Rheumatoid arthritis (RA) is a chronic autoimmune disease causing joint inflammation and destruction.
• Novel therapeutic targets are essential for improving RA treatment outcomes.

Purpose of the Study:

• To identify immune-related biomarkers for RA.
• To investigate CD27 as a potential therapeutic target for RA treatment.

Main Methods:

• Bioinformatics analysis of gene expression data from RA patients and healthy controls.
• Machine learning (LASSO, Boruta) to identify biomarkers.
• Validation in an independent dataset.
• Evaluation of CD27 neutralization in a collagen-induced arthritis (CIA) mouse model.
• Mechanistic studies using qPCR, Western blot, ELISA, and flow cytometry.

Main Results:

• Identified CD27, CD24, TNFRSF4, and PDCD1LG2 as potential RA biomarkers with strong diagnostic performance.
• CD27 neutralization significantly reduced arthritis severity in the CIA model.
• Therapeutic effect linked to suppression of Th1 responses and reduced Th1 cytokines (IFN-γ, IL-2, TNF-α).
• Mechanistically, CD27 neutralization modulated AKT and NF-κB signaling pathways.
• In vitro studies showed CD27 promotes Th1 differentiation.

Conclusions:

• CD27 is a potential therapeutic target for rheumatoid arthritis.
• CD27 neutralization attenuates RA severity by suppressing Th1 responses via AKT and NF-κB pathways.
• Findings offer new insights into RA pathogenesis and support CD27-targeted therapy.