| C‑reactive protein (CRP) is a highly conserved pentraxin-family acute‑phase protein synthesized predominantly by hepatocytes under transcriptional control of IL‑6, IL‑1β, and TNF, where it is secreted as a cyclic pentamer that circulates in plasma and acts as a pattern‑recognition molecule linking tissue injury and infection to complement activation and opsonophagocytic clearance. The native pentameric structure arranges five identical noncovalently associated subunits around a central pore, each subunit forming a β‑sandwich fold with a Ca²⁺‑dependent ligand‑binding site that recognizes phosphocholine, oxidized phospholipids, and neoepitopes on apoptotic cells, nuclear particles, and some bacterial surfaces; this modular architecture allows CRP to bind a wide spectrum of damage‑ and pathogen‑associated ligands with high avidity. Ligand‑bound CRP efficiently engages C1q to initiate the classical complement cascade and interacts with Fcγ receptors on phagocytes, which together promote opsonization, complement deposition, and phagocytic uptake of apoptotic bodies, necrotic debris, and microbes, and also drive local production of pro‑inflammatory cytokines that amplify the acute‑phase response. In vascular tissues and atheromatous plaques, CRP is detected in both its native pentameric and dissociated monomeric forms, and experimental data indicate that CRP can contribute directly to atherogenesis by promoting endothelial activation, monocyte recruitment, uptake of modified lipids, smooth muscle cell apoptosis, and thrombogenic changes, in addition to reflecting upstream inflammatory signaling. High‑sensitivity CRP measurement in serum provides a stable, reproducible index of low‑grade systemic inflammation, and large prospective cohort studies show that baseline CRP levels in otherwise healthy individuals independently predict future risk of myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death across a wide range of traditional risk factor profiles, with predictive power that is at least comparable to, and additive with, LDL cholesterol and Framingham risk scores. Elevated CRP also tracks with disease activity and joint damage in rheumatoid arthritis and other chronic inflammatory disorders. |
