C-reactive protein

C-reactive protein
C-reactive protein, pentraxin-related

Constructed from 1B09
Identifiers
Symbols CRP; MGC149895; MGC88244; PTX1
External IDs OMIM123260 MGI88512 HomoloGene476 GeneCards: CRP Gene
RNA expression pattern
PBB GE CRP 37020 at tn.png
PBB GE CRP 205753 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1401 12944
Ensembl ENSG00000132693 ENSMUSG00000037942
UniProt P02741 E9PZ20
RefSeq (mRNA) NM_000567.2 NM_007768.4
RefSeq (protein) NP_000558.2 NP_031794.3
Location (UCSC) Chr 1:
159.68 – 159.68 Mb
Chr 1:
174.63 – 174.63 Mb
PubMed search [1] [2]
This box: view · protein found in the blood, the levels of which rise in response to inflammation (i.e. C-reactive protein is an acute-phase protein). Its physiological role is to bind to phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system via the C1Q complex.[1]

CRP is synthesized by the liver[2] in response to factors released by fat cells (adipocytes).[3] It is a member of the pentraxin family of proteins.[2] It is not related to C-peptide or protein C. C-reactive protein was the first pattern recognition receptor (PRR) to be identified.[4]

Contents

History and nomenclature

CRP was so named because it was first discovered as a substance in the serum of patients with acute inflammation that reacted with the C- (capsular) polysaccharide of pneumococcus.

Discovered by Tillett and Francis in 1930 [5], it was initially thought that CRP might be a pathogenic secretion as it was elevated in people with a variety of illnesses including cancer,[2] however, discovery of hepatic synthesis demonstrated that it is a native protein.[6][7][8]

Genetics and biochemistry

The CRP gene is located on the first chromosome (1q21-q23). CRP is a 224-residue protein[9] with a monomer molar mass of 25106 Da. The protein is an annular pentameric disc in shape and a member of the small pentraxins family.

Function

The acute phase response develops in a wide range of acute and chronic inflammatory conditions like bacterial, viral, or fungal infections; rheumatic and other inflammatory diseases; malignancy; and tissue injury or necrosis. These conditions cause release of interleukin-6 and other cytokines that trigger the synthesis of CRP and fibrinogen by the liver. During the acute phase response, levels of CRP rapidly increase within 2 hours of acute insult, reaching a peak at 48 hours. With resolution of the acute phase response, CRP declines with a relatively short half-life of 18 hours. Measuring CRP level is a screen for infectious and inflammatory diseases. Rapid, marked increases in CRP occur with inflammation, infection, trauma and tissue necrosis, malignancies, and autoimmune disorders. Because there are a large number of disparate conditions that can increase CRP production, an elevated CRP level does not diagnose a specific disease. An elevated CRP level can provide support for the presence of an inflammatory disease, such as rheumatoid arthritis, polymyalgia rheumatica or giant-cell arteritis.

The physiological role of CRP is to bind to phosphocholine expressed on the surface of dead or dying cells (and some types of bacteria) in order to activate the complement system. CRP binds to phosphocholine on microbes and damaged cells and enhances phagocytosis by macrophages. Thus, CRP participates in the clearance of necrotic and apoptotic cells.

CRP is a member of the class of acute-phase reactants, as its levels rise dramatically during inflammatory processes occurring in the body. This increment is due to a rise in the plasma concentration of IL-6, which is produced predominantly by macrophages[2] as well as adipocytes.[3] CRP binds to phosphocholine on microbes. It is thought to assist in complement binding to foreign and damaged cells and enhances phagocytosis by macrophages (opsonin mediated phagocytosis), which express a receptor for CRP. It is also believed to play another important role in innate immunity, as an early defense system against infections.

CRP rises up to 50,000-fold in acute inflammation, such as infection. It rises above normal limits within 6 hours, and peaks at 48 hours. Its half-life is constant, and therefore its level is mainly determined by the rate of production (and hence the severity of the precipitating cause).

Serum amyloid A is a related acute-phase marker that responds rapidly in similar circumstances.[2]

Clinical significance

Scleroderma, polymyositis, and dermatomyositis often elicit little or no CRP response. CRP levels also tend not to be elevated in SLE unless serositis or synovitis is present. Elevations of CRP in the absence of clinically significant inflammation can occur in renal failure. CRP level is an independent risk factor for atherosclerotic disease. Patients with high CRP concentrations are more likely to develop stroke, myocardial infarction, and severe peripheral vascular disease.


Role in cardiovascular disease

Recent research suggests that patients with elevated basal levels of CRP are at an increased risk of diabetes,[10][11] hypertension and cardiovascular disease. A study of over 700 nurses showed that those in the highest quartile of trans fat consumption had blood levels of CRP that were 73% higher than those in the lowest quartile.[12] Although one group of researchers indicated that CRP may be only a moderate risk factor for cardiovascular disease,[13] this study (known as the Reykjavik Study) was found to have some problems for this type of analysis related to the characteristics of the population studied, and there was an extremely long follow-up time, which may have attenuated the association between CRP and future outcomes.[14] Others have shown that CRP can exacerbate ischemic necrosis in a complement-dependent fashion and that CRP inhibition can be a safe and effective therapy for myocardial and cerebral infarcts; so far, this has been demonstrated in animal models only.[15]

It has been hypothesized that a high CRP levels might reflect a large benefit from statins. This is based on the JUPITER trial that found that elevated CRP levels without hyperlipidemia benefited. Statins were selected because they have been proven to reduce levels of CRP.[2][16] A subsequent trial however failed to find that CRP was useful for determining statin benefit.[17]

To clarify whether CRP is a bystander or active participant in atherogenesis, a 2008 study compared people with various genetic CRP variants. Those with a high CRP due to genetic variation had no increased risk of cardiovascular disease compared to those with a normal or low CRP.[18] A study published in 2011 shows that CRP is associated with lipid responses to low-fat and high-polyunsaturated fat diets.[19]

Role in cancer

The role of inflammation in cancer is not well known. Some organs of the body show greater risk of cancer when they are chronically inflamed.[clarification needed]

Blood samples of persons with colon cancer have an average CRP concentration of 2.69 milligrams per liter. Persons without colon cancer average 1.97 milligrams per liter. The difference was statistically significant.[20] These findings concur with previous studies that indicate that anti-inflammatory drugs could lower colon cancer risk.[21]

Diagnostic use

CRP is used mainly as a marker of inflammation. Apart from liver failure, there are few known factors that interfere with CRP production.[2]

Measuring and charting CRP values can prove useful in determining disease progress or the effectiveness of treatments. Blood, usually collected in a serum-separating tube, is analysed in a medical laboratory or at the point of care. Various analytical methods are available for CRP determination, such as ELISA, immunoturbidimetry, rapid immunodiffusion, and visual agglutination.

References

  1. ^ Thompson, D; Pepys, MB; Wood, SP (February 1999). "The physiological structure of human C-reactive protein and its complex with phosphocholine". Structure 7 (2): 169–77. doi:10.1016/S0969-2126(99)80023-9. PMID 10368284. 
  2. ^ a b c d e f g h Pepys, MB; Hirschfield, GM (June 2003). "C-reactive protein: a critical update" (PDF). J Clin Invest 111 (12): 1805–12. doi:10.1172/JCI18921. PMC 161431. PMID 12813013. http://www.jci.org/articles/view/18921/files/pdf?disposition=attachment. 
  3. ^ a b Lau, DC; Dhillon, B; Yan, H; Szmitko, PE; Verma, S (May 2005). "Adipokines: molecular links between obesity and atheroslcerosis". Am J Physiol Heart Circ Physiol 288 (5): H2031–41. doi:10.1152/ajpheart.01058.2004. PMID 15653761. http://ajpheart.physiology.org/content/288/5/H2031.full.pdf. 
  4. ^ Mantovani A, Garlanda C, Doni A, Bottazzi B (January 2008). "Pentraxins in innate immunity: from C-reactive protein to the long pentraxin PTX3". J. Clin. Immunol. 28 (1): 1–13. doi:10.1007/s10875-007-9126-7. PMID 17828584. 
  5. ^ Tillett WS, Francis T (September 1930). "Serological reactions in pneumonia with a nonprotein somatic fraction of pneumococcus". J. Exp. Med. 52 (4): 561–71. doi:10.1084/jem.52.4.561. PMC 2131884. PMID 19869788. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2131884. 
  6. ^ Peter J. Kennelly; Murray, Robert F.; Victor W. Rodwell; Kathleen M. Botham (2009). Harper's illustrated biochemistry. McGraw-Hill Medical. ISBN 0-07-162591-7. 
  7. ^ Matthew R. Pincus; McPherson, Richard A.; Henry, John Bernard (2007). Henry's clinical diagnosis and management by laboratory methods. Saunders Elsevier. ISBN 1-4160-0287-1. 
  8. ^ John J. Ratey MD; Gary A. Noskin MEd MD; MD, Ralph Braun; Edward N. Hanley Jr MD; Iain B. McInnes; Shaun Ruddy MD (2008). Kelley's Textbook of Rheumatology: 2-Volume Set, Expert Consult: Online and Print (Textbook of Rheumatology (Kelley's)(2 Vol)). Philadelphia: Saunders. ISBN 1-4160-3285-1. 
  9. ^ NCBI Entrez Protein #CAA39671
  10. ^ Pradhan AD; Manson, JE; Rifai, N; Buring, JE; Ridker, PM (2001). "C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus". JAMA 286 (3): 327–34. doi:10.1001/jama.286.3.327. PMID 11466099. 
  11. ^ Dehghan A; Kardys, I; de Maat, MP; Uitterlinden, AG; Sijbrands, EJ; Bootsma, AH; Stijnen, T; Hofman, A et al. (March 2007). "Genetic variation, C-reactive protein levels, and incidence of diabetes". Diabetes 56 (3): 872–8. doi:10.2337/db06-0922. PMID 17327459. http://diabetes.diabetesjournals.org/content/56/3/872.full.pdf. 
  12. ^ Lopez-Garcia, E; Schulze, MB; Meigs, JB; Manson, JE; Rifai, N; Stampfer, MJ; Willett, WC; Hu, FB (March 2005). "Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction". J Nutr 135 (3): 562–6. PMID 15735094. http://jn.nutrition.org/content/135/3/562.full.pdf. 
  13. ^ John Danesh; Wheeler, JG; Hirschfield, GM; Eda, S; Eiriksdottir, G; Rumley, A; Lowe, GD; Pepys, MB et al. (2004). "C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease". N Engl J Med 350 (14): 1387–97. doi:10.1056/NEJMoa032804. PMID 15070788. 
  14. ^ Koenig, Wolfgang (2006). "C-reactive protein - a critical cardiovascular risk marker". CRPhealth.com.
  15. ^ Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, Hawkins PN, Myers RM, Smith MD, Polara A, Cobb AJ, Ley SV, Aquilina JA, Robinson CV, Sharif I, Gray GA, Sabin CA, Jenvey MC, Kolstoe SE, Thompson D, Wood SP (2006). "Targeting C-reactive protein for the treatment of cardiovascular disease". Nature 440 (7088): 1217–21. Bibcode 2006Natur.440.1217P. doi:10.1038/nature04672. PMID 16642000. 
  16. ^ Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ (November 2008). "Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein". N. Engl. J. Med. 359 (21): 2195–207. doi:10.1056/NEJMoa0807646. PMID 18997196. 
  17. ^ Jonathan Emberson, Jonathan Emberson, Jonathan Emberson, Jonathan Emberson, Jonathan Emberson, Jonathan Emberson, Jonathan Emberson (February 2011). "C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20,536 patients in the Heart Protection Study". Lancet 377 (9764): 469–76. doi:10.1016/S0140-6736(10)62174-5. PMC 3042687. PMID 21277016. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3042687. 
  18. ^ Zacho J, Tybjaerg-Hansen A, Jensen JS, Grande P, Sillesen H, Nordestgaard BG (October 2008). "Genetically elevated C-reactive protein and ischemic vascular disease". N. Engl. J. Med. 359 (18): 1897–908. doi:10.1056/NEJMoa0707402. PMID 18971492. 
  19. ^ St-Onge MP, Zhang S, Darnell B, Allison DB (April 2009). "Baseline serum C-reactive protein is associated with lipid responses to low-fat and high-polyunsaturated fat diets". J. Nutr. 139 (4): 680–3. doi:10.3945/jn.108.098251. PMC 2666362. PMID 19297430. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2666362. 
  20. ^ Erlinger TP, Platz EA, Rifai N, Helzlsouer KJ (February 2004). "C-reactive protein and the risk of incident colorectal cancer". Journal of the American Medical Association 291 (5): 585–90. doi:10.1001/jama.291.5.585. PMID 14762037. http://jama.ama-assn.org/content/291/5/585.full.pdf. 
  21. ^ Baron JA, et al. (2003). "A randomized trial of aspirin to prevent colorectal adenomas". N Engl J Med 348 (10): 891–9. doi:10.1056/NEJMoa021735. PMID 12621133. 
  22. ^ Clyne B, Olshaker JS (1999). "The C-reactive protein". J Emerg Med 17 (6): 1019–25. doi:10.1016/S0736-4679(99)00135-3. PMID 10595891. 
  23. ^ Lloyd-Jones DM, Liu K, Tian L, Greenland P (June 2006). "Narrative review: assessment of C-reactive protein in risk prediction for cardiovascular disease". Ann Intern Med 145 (1): 35–42. PMID 16818927. http://annals.org/cgi/content/full/0000605-200607040-00129v1. 

External links


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • C-reactive protein — Protéine C réactive Pour les articles homonymes, voir CRP. La protéine C réactive, plus couramment appelée C reactive protein ou CRP, est une protéine de phase aiguë exclusivement synthétisée par le foie. Elle joue un rôle important dans les… …   Wikipédia en Français

  • C-reactive protein — A protein of the pentraxin family found in serum in various disease conditions particularly during the acute phase of immune response. C reactive protein is synthesized by hepatocytes and its production may be triggered by prostaglandin E1 or… …   Dictionary of molecular biology

  • C-reactive protein (CRP) — A plasma protein that rises in the blood with the inflammation from certain conditions. C reactive protein is one of the plasma proteins known as acute phase proteins: proteins whose plasma concentrations increase (or decrease) by 25% or more… …   Medical dictionary

  • CRP (C-reactive protein) — A plasma protein that rises in the blood with the inflammation from certain conditions. C reactive protein is one of the plasma proteins known as acute phase proteins: proteins whose plasma concentrations increase (or decrease) by 25% or more… …   Medical dictionary

  • high-sensitivity C-reactive protein (hs-CRP) test — an extremely sensitive test to determine the level of C reactive protein in the blood; as the hs CRP rises, the risk of cardiovascular disease increases …   Medical dictionary

  • C-reactive protein — noun a byproduct of inflammation; a globulin that is found in the blood in some cases of acute inflammation • Syn: ↑CRP • Hypernyms: ↑serum globulin * * * ¦ ̷ ̷ (ˌ) ̷ ̷ ˌ ̷ ̷  ̷ ̷ noun Usage: usually capitalized C Etymology: C polysaccharide, a… …   Useful english dictionary

  • C-reactive protein — noun Etymology: C polysaccharide, a polysaccharide found in the cell wall of pneumococci and precipitated by this protein, from carbohydrate Date: 1955 a protein present in blood serum in various abnormal states (as inflammation or neoplasia) …   New Collegiate Dictionary

  • C-reactive protein — C re·ac·tive protein .sē rē .ak tiv n a protein produced by the liver that is normally present in trace amounts in the blood serum but is elevated during episodes of acute inflammation (as those associated with neoplastic disease, chronic… …   Medical dictionary

  • C-reactive protein — C re•ac•tive protein [[t]ˈsi riˌæk tɪv[/t]] n. biochem. a globulin that increases in concentration in the bloodstream during infectious states and other abnormal conditions Abbr.: CRP • Etymology: 1955–60; for C polysaccharide, which is… …   From formal English to slang

  • C-reactive protein — /see ree ak tiv/, Biochem. a globulin that increases in concentration in the bloodstream during infectious states and other abnormal conditions. Abbr.: CRP [1955 60; for C polysaccharide, which is precipitated by this protein] * * * …   Universalium

Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”