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Invisible marker of inflammation: the history and discovery of C-reactive protein!
C-reactive protein (CRP) is a ring-shaped pentameric protein found in plasma, whose concentration increases during inflammatory responses. As an acute phase protein, CRP is synthesized by the liver, usually after initiation of interleukin-6 (IL-6) released by macrophages and T cells. The physiological role of this protein includes binding to phosphatidylcholine expressed on the surface of necrotic or dying cells to activate the complement system.
CRP synthesis is constantly influenced by macrophages, T cells and adipocytes (fat tissue), and plays an important role in acute inflammation.
History and Etymology
CRP was first discovered in 1930 by two scientists, Tillett and Francis. Initially, CRP was considered a pathogenic secretion because its concentration is elevated in a variety of diseases, including cancer. As scientists delved deeper into CRP, they discovered that it is actually a native protein synthesized by the liver. The method of measuring CRP has also evolved with the advancement of technology, from the initial Quellung reaction to the current dynamic light scattering method, making the test more accurate.
CRP was named after its initial identification as a substance that reacts with pneumococcal cell wall polysaccharides in the serum of patients with acute inflammation.
Genes and Structure
CRP belongs to the pentraxin family. The encoded polypeptide contains 224 amino acids. The complete CRP protein is composed of five monomers with a total mass of about 120,000 Da. In serum, CRP presents a stable pentamer structure and is shaped like a disk.
Function
The main function of CRP is to bind to phosphatidylcholine expressed on the surface of bacterial cells, activate the complement system, promote the phagocytosis of macrophages, and then clear necrotic and apoptotic cells and bacteria. CRP also helps clear out oxygen-deprived cells, but doing so may cause these cells to be disposed of prematurely.
CRP binds to IgG antibodies by binding to Fc-gamma receptor IIa and initiates the classical complement pathway through C1q to form an immune complex.
Serum Levels
Measurement methods
Conventional CRP measurement methods can only detect a range of 10 to 1,000 mg/L, while high-sensitivity CRP (hs-CRP) can detect 0.5 to 10 mg/L. When hs-CRP is over 3 mg/L, it may indicate risk of cardiovascular disease, while below 1 mg/L is considered low risk.
Normal and acute inflammation
In healthy adults, the normal concentration range of CRP is 0.8 mg/L to 3.0 mg/L, but some healthy adults may still have CRP values as high as 10 mg/L. In acute inflammation, CRP levels can transiently rise to over 500 mg/L and peak 36 to 50 hours after injury or inflammation. Once inflammation is reduced, CRP levels also drop rapidly.
Clinical significanceIn the case of acute inflammation, CRP concentration can rise to 5 mg/L within 6 hours and reach a peak within 48 hours.
Diagnostic Uses
CRP is primarily used as an inflammatory marker. Although liver dysfunction may affect its production, other factors have limited impact. The measurement and graphing of CRP are important for determining the progression of a disease or the effectiveness of treatment. Methods such as immunoassay and radial immunodiffusion are also used for research purposes.
Cardiovascular Disease
Recent studies have shown that elevated CRP levels are associated with an increased risk of diabetes, hypertension, and cardiovascular disease. Some studies suggest that high CRP levels may be a risk factor for atherosclerosis.
Tumors and obstructive sleep apnea
The role of CRP in tumor development is unclear, but it has been linked to certain cancers. CRP has also been shown to be elevated in obstructive sleep apnea, with levels correlating with the severity of the condition.
As knowledge of CRP deepens, this invisible marker has become an important tool for understanding the body's inflammatory response and related diseases. So, how can we use CRP research to improve disease diagnosis and treatment in the future?
