CRP Is a Key Indicator of Rheumatoid Arthritis-Associated Vascular Injury and Neurodegeneration

Area of Science:

• Rheumatology
• Immunology
• Neurology

Background:

• Systemic inflammation is central to rheumatoid arthritis (RA) progression and comorbidities like cardiovascular disease (CVD) and Alzheimer's disease (AD).
• C-reactive protein (CRP) exists in pentameric (pCRP) and monomeric (mCRP) forms, with mCRP implicated as a proinflammatory mediator.

Purpose of the Study:

• To review the molecular mechanisms linking RA, its comorbidities, and the distinct roles of CRP isoforms.
• To explore the connection between inflammatory biomarkers, vascular integrity, and neurodegeneration in RA patients.

Main Methods:

• Narrative review of existing literature on systemic inflammation in RA.
• Analysis of molecular cross-talk between CRP isoforms, inflammatory cytokines, vascular markers, and neurodegenerative pathways.

Main Results:

• Monomeric C-reactive protein (mCRP) actively drives endothelial dysfunction, atherosclerosis, and synovial inflammation.
• Elevated cytokines (IL-6, TNF-α) and vascular injury contribute to cerebral small vessel disease (cSVD) and cognitive decline, indicated by neurofilament light chain (NfL).
• Central sensitization (CS) and neuroimmune signaling contribute to pain-independent joint swelling in RA.

Conclusions:

• Understanding CRP isoforms and neuronal markers can improve RA risk stratification.
• Targeting mCRP presents a potential therapeutic strategy for both articular and extra-articular manifestations of RA.