C-reactive protein

From Wikipedia, the free encyclopedia

C-reactive protein, pentraxin-related
CRP drawn from PDB 1B09
Available structures: 1b09, 1gnh, 1lj7
Identifiers
Symbol(s) CRP; MGC149895; MGC88244; PTX1
External IDs OMIM: 123260 MGI: 88512 HomoloGene: 476
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 1401 12944
Ensembl ENSG00000132693 ENSMUSG00000037942
Uniprot P02741 Q542I3
Refseq NM_000567 (mRNA)
NP_000558 (protein)		 NM_007768 (mRNA)
NP_031794 (protein)
Location Chr 1: 157.95 - 157.95 Mb Chr 1: 174.53 - 174.54 Mb
Pubmed search [3] [4]

C-reactive protein (CRP) is a protein produced as part of the inflammatory process. It is a routine test for heart failure; high levels of CRP may predict a bad outcome. (However, it is an unreliable test for heart failure, because inflammation from other causes also raises CRP.)

CRP is a plasma protein, an acute phase protein produced by the liver[1] and by adipocytes.[2] It is a member of the pentraxin family of proteins.[1] It is not related to C-peptide or protein C.

Contents

[edit] History and nomenclature

C-reactive protein was originally discovered by Tillett and Francis in 1930 as a substance in the serum of patients with acute inflammation that reacted with the C polysaccharide of pneumococcus.[3] Initially it was thought that CRP might be a pathogenic secretion, as it was elevated in people with a variety of illnesses, including carcinomas. Discovery of hepatic synthesis and secretion of CRP closed that debate. It is thought to bind to phosphocholine, thus initiating recognition and phagocytosis of damaged cells.[1]

[edit] Genetics and biochemistry

The CRP gene is located on the first chromosome (1q21-q23). CRP is a 224 residue protein[4] with a monomer molar mass of 25106 Da. The protein is an annular pentameric disc in shape. Proteins with this type of configuration are known as pentraxins. Native CRP is a bit different as it has 10-subunits making two pentameric discs, with an overall molecular mass of 251060 Da.[citation needed]

[edit] Function

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[1] as well as adipocytes.[2] CRP binds to phosphorylcholine on microbes. It is thought to assist in complement binding to foreign and damaged cells and enhances phagocytosis by macrophages, which express a receptor for CRP. It is also believed to play an 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.[1]

[edit] 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.[1]

Measuring and charting C-reactive protein 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 testing.

Various analytical methods are available for CRP determination, such as ELISA, immunoturbidimetry, rapid immunodiffusion and visual agglutination.

Viral infections tend to give a lower CRP level than bacterial infection.

[edit] Cardiology diagnostic test

Arterial damage is thought to result from inflammation due to chemical insults. 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.[5] 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.[1]

[edit] Glycosylation

CRP may have sugars—sialic acid, glucose, galactose and mannose—attached to it (i.e. it gets glycosylated.) In different disease states, one or two amino-acids get lopped off CRP. It retains its activity, but these losses open it up to glycosylation. Different diseases (each of which raise CRP) will add sugars to it in different patterns. The patterns are different across diseases, but similar amongst patients who had the same disease. A 2003 study looked at patients with lupus, leukemia, tuberculosis, leishmaniasis, Cushing's syndrome and bone cancer. (Healthy subjects did not have enough CRP to successfully characterize "normal" CRP.)

Previous work had shown that CRP increased the rate at which a particular parasite could invade blood cells. The study showed that the different CRPs had very different potencies in this regard. The authors speculate that subtyping CRP may give us more insight into heart attack mechanisms. Although this did not demonstrate whether this glycation of CRP was a 'good thing' or a 'bad thing', it offered circumstantial evidence that the differing glycation is part of CRPs mode-of-action.[6]

[edit] Role in cardiovascular disease

Recent research suggests that patients with elevated basal levels of CRP are at an increased risk for diabetes,[7][8] 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 C-reactive protein (CRP, a pro-inflammatory cytokine which is a cardiovascular disease risk factor) that were 73% higher than those in the lowest quartile.[9] Although one group of researchers indicated that CRP may only be a moderate risk factor for cardiovascular disease,[10] 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.[11] 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 only been demonstrated in animal models.[12]

To measure the CRP level, a "high-sensitivity" CRP or hs-CRP test needs to be performed and analyzed by a laboratory. This is an automated blood test designed for greater accuracy in measuring low levels of CRP, which allows the physician to assess cardiovascular risk. If a result in the low-risk range is found ( < 1 mg/L), it does not need repeating. Higher levels need repeating, and clinical evaluation as necessary.

[edit] 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.

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.[13] These findings concur with previous studies that indicate that anti-inflammatory drugs could lower colon cancer risk.[14]

[edit] See also

[edit] Additional images

C-reactive protein

[edit] References

  1. ^ a b c d e f g Pepys MB, Hirschfield GM (2003). "C-reactive protein: a critical update". J. Clin. Invest. 111 (12): 1805-12. doi:10.1172/JCI18921. PMID 12813013.  Full text at PMC: 161431
  2. ^ a b Lau DC, Dhillon B, Yan H, Szmitko PE, Verma S (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. 
  3. ^ Tillett WS, Francis Jr T (1930). "Serological reactions in pneumonia with a nonprotein somatic fraction of pneumococcus" (PDF). J Exp Med 52: 561-585. doi:10.1084/jem.52.4.561. 
  4. ^ NCBI Entrez Protein #CAA39671 [1]
  5. ^ Lloyd-Jones DM, Liu K, Tian L, Greenland P (2006). "Narrative Review: Assessment of C-Reactive Protein in Risk Prediction for Cardiovascular Disease". Ann Intern Med 145 (1): 35-42. PMID 16818927. 
  6. ^ Tanusree DAS et al. "Induction of glycosylation in human C-reactive protein under different pathological conditions" (pdf). Biochem. J. (2003) 373, 345–355. 
  7. ^ Pradhan AD (2001). "C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus". JAMA 286: 327–334. doi:10.1001/jama.286.3.327. PMID 11466099. 
  8. ^ Dehghan A (2007). "Genetic variation, C-reactive protein levels, and incidence of diabetes.". Diabetes 56: 872. doi:10.2337/db06-0922. PMID 17327459. 
  9. ^ Esther Lopez-Garcia (2005). "Consumption of Trans Fatty Acids Is Related to Plasma Biomarkers of Inflammation and Endothelial Dysfunction". The Journal of Nutrition 135 (3): 562–566. PMID 15735094. 
  10. ^ John Danesh (2004). "C-Reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart Disease". New England Journal of Medicine 350 (14): 1387–1397. doi:10.1056/NEJMoa032804. PMID 15070788. 
  11. ^ Koenig, Wolfgang (2006). C-Reactive Protein – A Critical Cardiovascular Risk Marker [2]
  12. ^ 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: 1217–1221. doi:10.1038/nature04672. PMID 16642000. 
  13. ^ Erlinger TP, Platz EA, Rifai N, Helzlsouer KJ (2004). "C-reactive protein and the risk of incident colorectal cancer". Journal of the American Medical Association 291 (Feb. 4): 585-590. PMID 14762037. 
  14. ^ Baron JA, et al (2003). "A randomized trial of aspirin to prevent colorectal adenomas". New England Journal of Medicine 348: 891-899. doi:10.1056/NEJMoa021735. PMID 12621133. 

[edit] External links

v • d • e
Proteins: albumin
Egg white
Serum albumin
Other
C-reactive protein - Lactalbumin - Parvalbumin - Ricin
v • d • e
Acute phase proteins
Amyloid
Other positive
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