C-reactive protein
C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin-6 secretion by macrophages and T cells. Its physiological role is to bind to lysophosphatidylcholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via C1q.[5]
Not to be confused with cAMP receptor protein.CRP is synthesized by the liver[6] in response to factors released by macrophages, T cells and fat cells (adipocytes).[7] It is a member of the pentraxin family of proteins.[6] It is not related to C-peptide (insulin) or protein C (blood coagulation). C-reactive protein was the first pattern recognition receptor (PRR) to be identified.[8]
History and etymology[edit]
Discovered by Tillett and Francis in 1930,[9] it was initially thought that CRP might be a pathogenic secretion since it was elevated in a variety of illnesses, including cancer.[6] The later discovery of hepatic synthesis (made in the liver) demonstrated that it is a native protein.[10][11][12] Initially, CRP was measured using the quellung reaction which gave a positive or a negative result. More precise methods nowadays use dynamic light scattering after reaction with CRP-specific antibodies.[13]
CRP was so named because it was first identified as a substance in the serum of patients with acute inflammation that reacted with the cell wall polysaccharide (C-polysaccharide) of pneumococcus.[14]
Genetics and structure[edit]
It is a member of the small pentraxins family (also known as short pentraxins).[15] The polypeptide encoded by this gene has 224 amino acids.[16] The full-length polypeptide is not present in the body in significant quantities due to signal peptide, which is removed by signal peptidase before translation is completed. The complete protein, composed of five monomers, has a total mass of approximately 120,000 Da. In serum, it assembles into stable pentameric structure with a discoid shape.[17]
C-reactive protein
Detection of inflammation in body.[24]
The amount of CRP in the blood.[24]
Serum levels[edit]
Measurement methods[edit]
Traditional CRP measurement only detected CRP in the range of 10 to 1,000 mg/L, whereas high sensitivity CRP (hs-CRP) detects CRP in the range of 0.5 to 10 mg/L.[25] hs-CRP can detect cardiovascular disease risk when in excess of 3 mg/L, whereas below 1 mg/L would be low risk.[26] Traditional CRP measurement is faster and less costly than hs-CRP, and can be adequate for some applications, such as monitoring hemodialysis patients.[27]
Normal[edit]
In healthy adults, the normal concentrations of CRP varies between 0.8 mg/L and 3.0 mg/L. However, some healthy adults show elevated CRP at 10 mg/L. CRP concentrations also increase with age, possibly due to subclinical conditions. There are also no seasonal variations of CRP concentrations. Gene polymorphism of interleukin-1 family, interleukin 6, and polymorphic GT repeat of the CRP gene do affect the usual CRP concentrations when a person does not have any medical illnesses.[6]
Acute inflammation[edit]
When there is a stimulus, the CRP level can increase 10,000-fold from less than 50 μg/L to more than 500 mg/L. Its concentration can increase to 5 mg/L by 6 hours and peak at 48 hours. The plasma half-life of CRP is 19 hours, and is constant in all medical conditions.[28] Therefore, the only factor that affects the blood CRP concentration is its production rate, which increases with inflammation, infection, trauma, necrosis, malignancy, and allergic reactions. Other inflammatory mediators that can increase CRP are TGF beta 1, and tumor necrosis factor alpha. In acute inflammation, CRP can increase as much as 50 to 100 mg/L within 4 to 6 hours in mild to moderate inflammation or an insult such as skin infection, cystitis, or bronchitis. It can double every 8 hours and reaches its peak at 36 to 50 hours following injury or inflammation. CRP between 100 and 500 mg/L is considered highly predictive of inflammation due to bacterial infection. Once inflammation subsides, CRP level falls quickly because of its relatively short half-life.[13]
Metabolic inflammation[edit]
CRP concentrations between 2 and 10 mg/L are considered as metabolic inflammation: metabolic pathways that cause arteriosclerosis[29] and type II diabetes mellitus[30]
Clinical significance[edit]
Diagnostic use[edit]
CRP is used mainly as an inflammation marker. Apart from liver failure, there are few known factors that interfere with CRP production.[6] Interferon alpha inhibits CRP production from liver cells which may explain the relatively low levels of CRP found during viral infections compared to bacterial infections [31][32]
Measuring and charting CRP values can prove useful in determining disease progress or the effectiveness of treatments. ELISA, immunoturbidimetry, nephelometry, radial immunodiffusion[33][26]
C-reactive protein
C-reactive protein
