C-reactive protein

From Wikipedia, the free encyclopedia

C-reactive protein, pentraxin-related

Constructed from 1B09

Available structures
Ortholog search: PDBe, RCSB
PDB
[show]List of PDB id codes
Identifiers
Symbols CRP ; PTX1
External OMIM: 123260 MGI: 88512
IDs

HomoloGene: 128039 GeneCards: CRP Gene

[show]Gene ontology
RNA expression pattern

More reference expression data

Orthologs
Species Human

Mouse

Entrez 1401

12944

Ensembl ENSG00000132693 ENSMUSG00000037942

UniProt P02741
RefSeq
(mRNA)
RefSeq
(protein)

P14847

NM_000567

NM_007768

NP_000558

NP_031794

Location Chr 1:

Chr 1:

(UCSC) 159.68 159.68 Mb 172.7 172.7 Mb

PubMed
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C-reactive protein (CRP) is an annular (ring-shaped), pentameric protein found in the blood
plasma, 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 lysophosphatidylcholine 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 macrophages and fat cells
(adipocytes).[3] It is a member of the pentraxin family of proteins.[2] It is not related to Cpeptide (insulin) or protein C (blood coagulation). C-reactive protein was the first pattern
recognition receptor (PRR) to be identified.[4]

Contents

1 History and nomenclature

2 Genetics and structure

3 Function

4 Clinical significance
o 4.1 Diagnostic use
o 4.2 Cancer

o 4.3 Cardiovascular disease

o 4.4 Fibrosis and inflammation
o 4.5 Obstructive sleep apnea
o 4.6 Coronary heart disease risk

5 See also

6 Additional images

7 References

8 External links

History and nomenclature

CRP was so named because it was first identified as a substance in the serum of patients with
acute inflammation that reacted with the C-polysaccharide of Pneumococcus.
Discovered by Tillett and Francis in 1930,[5] it was initially thought that CRP might be a
pathogenic secretion since it was elevated in a variety of illnesses, including cancer.[2] The
later discovery of hepatic synthesis demonstrated that it is a native protein.[6][7][8]

Genetics and structure

The CRP gene is located on the first chromosome (1q21-q23). It is a member of the small
pentraxins family. It has 224 amino acids,[9] has a monomer molecular mass of 25106 Da, and
has an annular pentameric discoid shape.

Function
CRP binds to the phosphocholine expressed on the surface of dead or dying cells and some
bacteria. This activates the complement system, promoting phagocytosis by macrophages,
which clears necrotic and apoptotic cells and bacteria.
This so-called acute phase response occurs as a result of a rise in the concentration of IL-6,
which is produced by macrophages[2] as well as adipocytes[3] in response to a wide range of
acute and chronic inflammatory conditions such as bacterial, viral, or fungal infections;
rheumatic and other inflammatory diseases; malignancy; and tissue injury and necrosis.
These conditions cause release of interleukin-6 and other cytokines that trigger the synthesis
of CRP and fibrinogen by the liver. .
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 plays a role in innate immunity as an
early defense system against infections.

CRP rises within two hours of the onset of inflammation, up to a 50,000-fold, and peaks at 48
hours. Its half-life of 48 hours is constant, and therefore its level is determined by the rate of
production and hence the severity of the precipitating cause. CRP is thus a screen for
inflammation.

Clinical significance
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. ELISA, immunoturbidimetry, rapid immunodiffusion, and visual
agglutination are all methods used to measure CRP.

Reference ranges for blood tests, showing C-reactive protein in brown-yellow in center.
A high-sensitivity CRP (hs-CRP) test measures low levels of CRP using laser nephelometry.
The test gives results in 25 minutes with a sensitivity down to 0.04 mg/L.
Normal concentration in healthy human serum is usually lower than 10 mg/L, slightly
increasing with aging. Higher levels are found in late pregnant women, mild inflammation
and viral infections (1040 mg/L), active inflammation, bacterial infection (40200 mg/L),
severe bacterial infections and burns (>200 mg/L).[10]
CRP is a more sensitive and accurate reflection of the acute phase response than the ESR[11]
(Erythrocyte Sedimentation Rate). ESR may be normal and CRP elevated. CRP returns to
normal more quickly than ESR in response to therapy.
Several studies investigated differential diagnostic values of CRP in a series of inflammatory
disease ( including inflammatory bowel disease, Intestinal Lymphoma, Intestinal
Tuberculosis and Behcet's Syndrome), and compared CRP to other inflammatory biomarkers,
such as ESR and WBC.[11]

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.[12] 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.[13]
In a 2004 prospective cohort study on colon cancer risk associated with CRP levels, people
with colon cancer had higher average CRP concentrations than people without colon cancer.
[14]
It can be noted that the average CRP levels in both groups were well within the range of

CRP levels usually found in healthy people. However, these findings may suggest that low
inflammation level can be associated with a lower risk of colon cancer, concurring with
previous studies that indicate anti-inflammatory drugs could lower colon cancer risk.[15]

Cardiovascular disease
Recent research suggests that patients with elevated basal levels of CRP are at an increased
risk of diabetes,[16][17] 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.[18] Although one group of researchers
indicated that CRP may be only a moderate risk factor for cardiovascular disease,[19] 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.[20] Others have shown that CRP can exacerbate ischemic necrosis in a complementdependent 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.[21]
It has been hypothesized that patients with high CRP levels might benefit from use of 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][22] Studies comparing effect of various statins in hs-CRP revealed similar
effects of different statins.[23][24] A subsequent trial however failed to find that CRP was useful
for determining statin benefit.[25]
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.[26]
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.[27] A study published in 2011 shows that CRP is associated with lipid responses to
low-fat and high-polyunsaturated fat diets.[28]

Fibrosis and inflammation

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.[29] Elevated level of CRP can also be observed in inflammatory bowel
disease (IBD), including Crohn's disease and ulcerative colitis.[11]

Obstructive sleep apnea

C-reactive protein (CRP), a marker of systemic inflammation, is also increased in obstructive
sleep apnea (OSA). CRP and interleukin-6 (IL-6) levels were significantly higher in patients

with OSA compared to obese control subjects.[30] Patients with OSA have higher plasma CRP
concentrations that increased corresponding to the severity of their apnea-hypopnea index
score. Treatment of OSA with CPAP (continuous positive airway pressure) significantly
alleviated the effect of OSA on CRP and IL-6 levels.[30]

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.[31] 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;[2] 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.[32]
The American Heart Association and U.S. Centers for Disease Control and Prevention have
defined risk groups as follows:[33]

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
cholesterol, LDL-C, triglycerides, and glucose level. Smoking, hypertension and
diabetes also increase the risk level of cardiovascular disease.

http://www.webmd.com/a-to-z-guides/c-reactive-protein-crp

Information and Resources

C-Reactive Protein (CRP)
Share this:
A C-reactive protein (CRP) test is a blood test that measures the amount of a protein called Creactive protein in your blood. C-reactive protein measures general levels of inflammation in
your body.
High levels of CRP are caused by infections and many long-term diseases. But a CRP test
cannot show where the inflammation is located or what is causing it. Other tests are needed to
find the cause and location of the inflammation.

Why It Is Done
A C-reactive protein (CRP) test is done to:

Check for infection after surgery. CRP levels normally rise within 2 to 6 hours of
surgery and then go down by the third day after surgery. If CRP levels stay elevated 3
days after surgery, an infection may be present.

Identify and keep track of infections and diseases that cause inflammation, such as:
o Cancer of the lymph nodes (lymphoma).
o Diseases of the immune system, such as lupus.
o Painful swelling of the blood vessels in the head and neck (giant cell arteritis).
o Painful swelling of the tissues that line the joints (rheumatoid arthritis).
o Swelling and bleeding of the intestines (inflammatory bowel disease).
o Infection of a bone (osteomyelitis).

Check to see how well treatment is working, such as treatment for cancer or for an
infection. CRP levels go up quickly and then become normal quickly if you are
responding to treatment measures.

A special type of CRP test, the high-sensitivity CRP test (hs-CRP), may be done to help find
out your risk of a heart attack and stroke. The results can help you and your doctor make
decisions about how to lower your risk. The connection between hs-CRP levels and the risk
of heart attack and stroke are not understood completely. But high levels may mean that the
lining of your arteries are inflamed. This may damage the arteries and raise your risk of a
heart attack and stroke.

Results
A C-reactive protein (CRP) test is a blood test that measures the amount of a protein called Creactive protein in your blood.
Normal
The normal values listed herecalled a reference rangeare just a guide. These ranges vary
from lab to lab, and your lab may have a different range for what's normal. Your lab report
should contain the range your lab uses. Also, your doctor will evaluate your results based on
your health and other factors. This means that a value that falls outside the normal values
listed here may still be normal for you or your lab.
Results are usually available within 24 hours.

C-reactive protein (CRP) 1

Less than 1.0 milligram per deciliter (mg/dL) or less than
10 milligrams per liter (mg/L)

Normal:

Any condition that results in sudden or severe inflammation may increase your CRP levels.
Some medicines may decrease your CRP levels.
Many conditions can change CRP levels. Your doctor will talk with you about any abnormal
results that may be related to your symptoms and past health.
High-sensitivity C-reactive protein (hs-CRP) levels
High-sensitivity C-reactive protein (hs-CRP) measures very low amounts of CRP in the
blood. This test may help find your risk of heart problems, especially when it is considered
along with other risk factors such as cholesterol, age, blood pressure, and smoking. It may be
done to find out if you have an increased chance of having a sudden heart problem, such as a
heart attack or stroke. But the connection between high CRP levels and heart disease risk is
not understood very well.
High-sensitivity C-reactive protein (hs-CRP) level 1
Normal:

Less than 0.1 mg/dL or less than 1 mg/L

hs-CRP level and heart disease risk 2

Less than 1.0 mg/L

1.0 to 3.0 mg/L

More than 3.0 mg/L

Low risk

Average risk

High risk

What Affects the Test

You may not be able to have the test or the results may not be helpful if:

You have just exercised.

You have an infection.

You have an intrauterine device (IUD) in place.

You are pregnant.

You are very overweight (obese).

C-Reactive Protein
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Also known as: CRP
Formal name: C-Reactive Protein
Related tests: Erythrocyte Sedimentation Rate (ESR); Complement; Procalcitonin; ANA;
Rheumatoid Factor
Were you looking for the high-sensitivity CRP (hs-CRP) test, used to assess your risk of
cardiovascular disease?

At a Glance

Test Sample

The Test

Common Questions

Ask Us

Related Pages

The Test
1. How is it used?
2. When is it ordered?
3. What does the test result mean?
4. Is there anything else I should know?

How is it used?
C-reactive protein (CRP) is a non-specific test. It is used by a doctor to detect inflammation if
there is a high suspicion of tissue injury or infection somewhere in the body, but the test
cannot tell where the inflammation is or what condition is causing it. CRP is not diagnostic of
any condition, but it can be used together with signs and symptoms and other tests to evaluate
an individual for an acute or chronic inflammatory condition.
For example, CRP may be used to detect or monitor significant inflammation in an individual
who is suspected of having an acute condition such as:

A serious bacterial infection like sepsis or a fungal infection

Pelvic inflammatory disease (PID)

The CRP test is useful in monitoring people with chronic inflammatory conditions to detect
flare-ups and/or to determine if treatment is effective. Some examples include:

Inflammatory bowel disease

Some forms of arthritis

Autoimmune diseases, such as lupus or vasculitis

CRP may sometimes be ordered along with an Erythrocyte Sedimentation Rate (ESR),
another test that detects inflammation. While the CRP test is not specific enough to diagnose
a particular disease, it does serve as a general marker for infection and inflammation, thus
alerting medical professionals that further testing and treatment may be necessary. Depending
on the suspected cause, a number of other tests may be performed to identify the source of
inflammation.
^ Back to top

When is it ordered?
This test may be ordered when an individual is suspected of having a serious bacterial
infection based on their medical history and signs and symptoms. It may be ordered, for
example, when a newborn shows signs of infection or when an individual has symptoms of
sepsis, such as fever, chills and rapid breathing and heart rate.
It may also be ordered on a regular basis to monitor conditions such as rheumatoid arthritis
and lupus and is often repeated at intervals to determine whether treatment is effective. This
is particularly useful for inflammation problems since CRP levels drop as inflammation
subsides.
^ Back to top

What does the test result mean?

The level of CRP in the blood is normally low.

A high or increasing amount of CRP in the blood suggests the presence of inflammation but
will not identify its location or the condition causing it. In individuals suspected of having a
serious bacterial infection, a high CRP suggests the presence of one. In people with chronic
inflammatory conditions, high levels of CRP suggest a flare-up or that treatment has not been
effective.
If the CRP level is initially elevated and drops, then it means that the inflammation or
infection is subsiding and/or responding to treatment.
^ Back to top

Is there anything else I should know?

CRP levels can be elevated in the later stages of pregnancy as well as with use of birth
control pills or hormone replacement therapy (i.e., estrogen). Higher levels of CRP have also
been observed in people who are obese.
The erythrocyte sedimentation rate (ESR) test will also be increased in the presence of
inflammation; however, CRP increases sooner and then decreases more rapidly than the ESR.

C-Reactive Protein
More Sharing Services Share on print Share on email
Share on twitter Share on facebook
Share this page:
Was this page helpful?
Also known as: CRP
Formal name: C-Reactive Protein
Related tests: Erythrocyte Sedimentation Rate (ESR); Complement; Procalcitonin; ANA;
Rheumatoid Factor
Were you looking for the high-sensitivity CRP (hs-CRP) test, used to assess your risk of
cardiovascular disease?

At a Glance

Test Sample

The Test

Common Questions

Ask Us

Related Pages

Common Questions
1. What are chronic inflammatory diseases?
2. What is the difference between CRP and hs-CRP tests?
3. Should everyone have a CRP test?
4. Can a CRP test be performed in my doctor's office?

1. What are chronic inflammatory diseases?

"Chronic inflammatory diseases" is a non-specific term used to characterize long-lasting or
frequently recurring bouts of inflammation associated with a more specific disease. Chronic
inflammation can be caused by a number of different pathological conditions such as arthritis,
lupus, or inflammatory bowel disease (Crohn disease or ulcerative colitis).
^ Back to top

2. What is the difference between CRP and hs-CRP tests?

Both tests are essentially the same, measuring the same substance in the blood. However, the
high sensitivity CRP (hs-CRP) test measures very small amounts of CRP in the blood and is
ordered most frequently for seemingly healthy people to assess their potential risk for heart
problems. It typically measures CRP in the range from 0.5 to 10 mg/L. The regular CRP test
is ordered for those at risk for infections or chronic inflammatory diseases (see Question #1).
It measures CRP in the range from 10 to 1000 mg/L.
^ Back to top

3. Should everyone have a CRP test?

The regular CRP test is not intended to be a general screening test, and many people will
never have one done. It is specifically used to detect inflammation and significant bacterial
infections.
^ Back to top

4. Can a CRP test be performed in my doctor's office?

It may be performed in a larger doctor's clinic, but most CRP tests will be performed in a
laboratory.