Structure and function of CRP ,CRP test and its clinical significance :
During Corona pandemic common people became aware of certain medical terms and words .One of them is C- reactive protein(CRP)test. In this article we shall know about what CRP is and what is clinical significance of CRP test,a blood test.
CRP is measured using a small blood sample drawn from a vein in patient's arm.
Doctor might order a CRP test if one has symptoms of inflammation. Doctors also use CRP levels to guide treatment of a bacterial inflections or to monitor inflammatory processes that occur in some autoimmune diseases.
Structure of CRP: C-reactive protein (CRP) is produced by the liver. It is a native protein. The level of CRP rises when there is inflammation throughout the body. It is one of a group of proteins, called acute phase reactants, that go up in response to inflammation. The levels of acute phase reactants increase in response to certain inflammatory proteins called Cytokines. These proteins are produced by white blood cells(Macrophages) during inflammation. Macrophages are type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells.
C-reactive protein (CRP) is an ring-shaped pentameric protein found in blood plasma. It is a member of the small pentraxins family. The monomer is consist of 224 amino acids, and molecular weight of 25,106 Da. The complete Pentameric protein, composed of five monomers(polypeptide chains) , has a total M.W. of approximately 125,000 Dalton. In serum, it assembles into stable pentameric structure with a discoid shape. C-reactive protein was the first pattern recognition receptor (PRR) to be identified.The CRP gene encoding for CRP is located on chromosome 1 (1q23).
Mechanism of action of CRP:Its circulating concentrations rise in response to the inflammation. The concentration of CRP increases in the conditions such as bacterial, viral or fungal infections; rheumatic and other inflammatory diseases; malignancy; and tissue injury and necrosis. It is synthesized by liver.
IL-6 and Cytokins are produced by macrophages,T cells as well as fat cells (adipocytes) in response to a wide range of acute and chronic inflammatory conditions.
Interleukin 6 is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. osteoclasts are large multinucleate bone cells which breaks down bine tissues and absorbs bone tissue during growth and healing. Osteoclasts are responsible for aged bone resorption and osteoblasts are responsible for new bone formation
Interleukin 6 (IL-6), promptly and transiently produced in response to infections and tissue injuries, contributes to host defense through the stimulation of acute phase responses, hematopoiesis, and immune reactions.
Therefore, IL-6 serum levels greater than 35 pg/mL of IL-6 are associated with increased risk of mortality, mechanical ventilation requirements, and increased severity of SARS-CoV-2 induced pneumonia.
Now interleukin-6 and other cytokines in turn triggers the synthesis of CRP and fibrinogen by the liver.The physiological role of CRP is to bind to phosphocholin i e. lysophosphatidylcholine expressed on the surface of dead or dying cells (pathogenic bacteria e.g Pneumococci) in order to activate the complement system via C1. This in turn activates the complement system, promoting phagocytosis by macrophages, which clears necrotic and apoptotic cells and bacteria.Apoptosis is the process of programmed cell death. It is used during early development to eliminate unwanted cells.
This so-called acute phase response occurs as a result of increasing concentrations of CRP binds to phosphocholine on surface of micro-organisms. 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.
A C-reactive protein test measures the level of C-reactive protein (CRP) in the blood. CRP is a protein made by liver. It's sent into bloodstream in response to inflammation. Inflammation is body's way of protecting tissues if you've been injured or have an infection. It can cause pain, redness, and swelling in the injured or affected area. Some autoimmune disorders and chronic diseases can also cause inflammation.
Normally, there is low levels of C-reactive protein in the blood. High levels may be sign of a serious infection or other disorder.
Significance of CRP test:
A CRP test may be used to find or monitor conditions that cause inflammation. These include:
Bacterial infections, such as sepsis, a severe and sometimes life-threatening condition.
A fungal infection.
Inflammatory bowel disease, a disorder that causes swelling and bleeding in the intestines.
An autoimmune disorder such as lupus or rheumatoid arthritis.
An infection of the bone called osteomyelitis.
Osteomyelitis is inflammation or swelling that occurs in the bone. It can result from an infection somewhere else in the body that has spread to the bone, or it can start in the bone — often as a result of an injury. Osteomyelitis is more common in younger children (five and under) but can happen at any age.
CRP test is required in following conditions:
The patient may need this test if he has symptoms of a serious bacterial infection. Symptoms include: Fever,Chills,Rapid breathing, Rapid heart rate,Nausea and vomiting.
If patient has already been diagnosed with an infection or have a chronic disease, this test may be used to monitor treatment. CRP levels rise and fall depending on how much inflammation
one has. If CRP levels go down, it's a sign that the treatment for inflammation is working.
Laboratory procedure for CRP estimation:
CRP is measured using a small blood sample drawn from a vein in patient's arm.
Measuring and charting CRP values can prove useful in determining the disease progress or the effectiveness of treatments.
The available method in detection of CRP:
Currently, immunoassays and related techniques are considered as major analytical methods with respect to the detection of CRP. The techniques typically include radioimmunoassay, enzyme immunoassay , chemiluminescence immunoassay , and fluorescence immunoassay.
CRP latex test:
The CRP-Latex is a slide agglutination test for the qualitative and semi-quantitative detection of C – Reactive Proteins (CRP) in human serum. Latex particles coated with goat IgG anti-human CRP are agglutinated when mixed with samples containing CRP.
CRP concentrations are calculated by using a calibration curve. Data reduction of the signals is performed by using a storable logit-log function for the calibration curve. These assays are performed on a Behring Nephelometer for quantitative CRP determination.
Range of CRP values:
(1) Low: hs-CRP level under 1.0 mg/L
(2) Average: between 1.0 and 3.0 mg/L
(3) High: above 3.0 mg/L
Dr Bhairavsinh Raol
