C-reactive protein
CRP | |||
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Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process |
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Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 1: 159.71 – 159.71 Mb | Chr 1: 172.53 – 172.66 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
C-reactive protein (CRP) is an annular (ring-shaped)
CRP is synthesized by the
History and etymology
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
Genetics and structure
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]
Function
CRP binds to the
This so-called
CRP binds to phosphocholine on micro-organisms. It is thought to assist in
Serum levels
C-reactive protein | |
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Purpose | Detection of inflammation in body.[24] |
Test of | The amount of CRP in the blood.[24] |
Measurement methods
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
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
Acute inflammation
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.
Metabolic inflammation
CRP concentrations between 2 and 10 mg/L are considered as metabolic inflammation: metabolic pathways that cause
Clinical significance
Diagnostic use
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.
]- low: hs-CRP level under 1.0 mg/L
- average: between 1.0 and 3.0 mg/L
- high: above 3.0 mg/L
Normal levels increase with
CRP cut-off levels indicating bacterial from non-bacterial illness can vary due to
CRP is a more sensitive and accurate reflection of the acute phase response than the ESR[37] (erythrocyte sedimentation rate). ESR may be normal while CRP is elevated. CRP returns to normal more quickly than ESR in response to therapy.[citation needed]
Cardiovascular disease
Recent research suggests that patients with elevated basal levels of CRP are at an increased risk of
It has been hypothesized that patients with high CRP levels might benefit from use of
In a meta-analysis of 20 studies involving 1,466 patients with coronary artery disease, CRP levels were found to be reduced after exercise interventions. Among those studies, higher CRP concentrations or poorer lipid profiles before beginning exercise were associated with greater reductions in CRP.[50]
To clarify whether CRP is a bystander or active participant in
Coronary heart disease risk
Arterial damage results from white blood cell invasion and inflammation within the wall. CRP is a general marker for inflammation and infection, so it can be used as a very rough proxy for heart disease risk. Since many things can cause elevated CRP, this is not a very specific prognostic indicator.[53][54] Nevertheless, a level above 2.4 mg/L has been associated with a doubled risk of a coronary event compared to levels below 1 mg/L;[6] however, the study group in this case consisted of patients who had been diagnosed with unstable angina pectoris; whether elevated CRP has any predictive value of acute coronary events in the general population of all age ranges remains unclear. Currently, C-reactive protein is not recommended as a cardiovascular disease screening test for average-risk adults without symptoms.[55]
The American Heart Association and U.S. Centers for Disease Control and Prevention have defined risk groups as follows:[56][26]
- Low Risk: less than 1.0 mg/L
- Average risk: 1.0 to 3.0 mg/L
- High risk: above 3.0 mg/L
But hs-CRP is not to be used alone and should be combined with elevated levels of
Fibrosis and inflammation
High levels of CRP has been associated to point mutation Cys130Arg in the APOE gene, coding for apolipoprotein E, establishing a link between lipid values and inflammatory markers modulation.[59][unreliable medical source?][58]
Cancer
The role of inflammation in cancer is not well understood. Some organs of the body show greater risk of cancer when they are chronically inflamed.[60] While there is an association between increased levels of C-reactive protein and risk of developing cancer, there is no association between genetic polymorphisms influencing circulating levels of CRP and cancer risk.[61]
In a 2004
Obstructive sleep apnea
C-reactive protein (CRP), a marker of systemic inflammation, is also increased in
Rheumatoid arthritis
In the context of rheumatoid arthritis (RA), CRP is one of the acute phase reactants, whose assessment is defined as part of the joint 2010 ACR/EULAR classification criteria for RA with abnormal levels accounting for a single point within the criteria [65] Higher levels of CRP are associated with more severe disease and a higher likelihood of radiographic progression. Rheumatoid arthritis associated antibodies together with 14-3-3η YWHAH have been reported to complement CRP in predicting clinical and radiographic outcomes in patients with recent onset inflammatory polyarthritis.[66] Elevated levels of CRP appear to be associated with common comorbidities including cardiovascular disease, metabolic syndrome, diabetes and interstitial lung (pulmonary) disease. Mechanistically, CRP also appears to influence osteoclast activity leading to bone resorption and also stimulates RANKL expression in peripheral blood monocytes.[67]
It has previously been speculated that single-nucleotide polymorphisms in the CRP gene may affect clinical decision-making based on CRP in rheumatoid arthritis, e.g. DAS28 (Disease Activity Score 28 joints). A recent study showed that CRP genotype and haplotype were only marginally associated with serum CRP levels and without any association to the DAS28 score.[68] Thus, that DAS28, which is the core parameter for inflammatory activity in RA, can be used for clinical decision-making without adjustment for CRP gene variants.[citation needed]
Viral infections
Increased blood CRP levels were higher in people with
Additional images
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C-reactive protein
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C-reactive protein
References
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- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037942 - Ensembl, May 2017
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External links
- MedlinePlus Encyclopedia: C-reactive protein
- Inflammation, Heart Disease and Stroke: The Role of C-Reactive Protein (American Heart Association)
- C-Reactive+Protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- CRP: analyte monograph - The Association for Clinical Biochemistry and Laboratory Medicine
- George Vrousgos, N.D. - Southern Cross University Archived 2020-02-18 at the Wayback Machine
- Human CRP genome location and CRP gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P02741 (C-reactive protein) at the PDBe-KB.