Acute-phase protein (Acute Phase Reactants)

1. Acute-phase proteins are raised in inflammatory conditions; these may be called:
   1. Acute inflammatory response pattern.
   2. Acute stress pattern.
   3. Acute-phase protein pattern.
   4. Acute stress pattern.
2. When there is an increase in an acute-phase protein, it is referred to as a positive acute-phase response.
   • In the case of a decrease in the acute-phase protein, it is referred to as a negative-phase protein.
3. The acute phase proteins (positive) are proteins whose concentration increases in the plasma, and after the disease episode is over, it decreases and may become normal.

C-Reactive Protein (CRP)

What sample is needed for C-Reactive Protein (CRP)?

1. The patient’s venous blood is needed to prepare the serum.
2. A fasting sample is preferred.
3. A random sample can be taken.
4. Analyze the fresh sample.
   1. Or it can be stored at 4 °C for <72 hours.
   2. At -20 °C for six months.

What are the Indications for C-Reactive Protein (CRP)?

1. Advised on bacterial infection.
2. It is advised for rheumatic fever.
3. It is advised in rheumatoid arthritis.
4. It may be advised after the surgery.
5. This is done in inflammatory diseases like acute rheumatic fever, rheumatoid arthritis, and bacterial infection.
6. It will help in the diagnosis of coronary artery disease.
7. This test can be done to diagnose bacterial endocarditis.
8. To diagnose appendicitis.
9. To diagnose active collagen vascular diseases.

What are the precautions for C-Reactive Protein (CRP)?

1. This may be raised in cigarette smoking.
2. Avoid hemolysed and lipemic samples.
3. Raised values are seen in hypertension, diabetes mellitus, metabolic syndrome, gingivitis, and bronchitis.
4. Decreased values are observed in weight loss, moderate alcohol consumption, and regular exercise.
5. Estrogens and progesterone increase C-reactive protein (CRP).
6. Niacin, statins, and fibrates decrease the C-Reactive Protein (CRP).
7. Keep in mind that:
   1. Cigarette smoking may increase the level.
   2. Estrogen and progesterone may increase the level.
   3. Niacin and statins may decrease the value.
   4. There may be an increased level of CRP in hypertension, diabetes mellitus, and metabolic syndrome.
8. Avoid lipemic or hemolyzed samples.

How will you define C-Reactive Protein (CRP)?

1. CRP is produced in the liver, and its name is derived from its reaction with streptococcal capsular polysaccharides (capsule).
2. CRP levels supporting the diagnosis of bacterial endocarditis, appendicitis, and active collagen diseases were>10 mg/L.
3. CRP molecular weight is ∼115 kDa.
4. It is synthesized in the liver and has little or no carbohydrates.

3. There are changes in the plasma protein in response to:
   1. Acute illness.
   2. Trauma.
   3. Necrosis.
   4. Infarction.
   5. Burns.
   6. Chemical injury.
   7. Malignant tumors.
4. The acute reaction protein pattern is also called:
   1. Acute inflammatory response pattern.
   2. Acute stress pattern.
   3. Acute-phase protein pattern.

What is the history of C-Reactive Protein (CRP)?

1. In 1930, Tillet and Francis found substance in the sera of acutely ill patients.
2. CRP  was given its name in 1941 because it is a protein.
3. This substance binds the C-polysaccharides of the cell wall of Strept. pneumomiae.
4. This leads to the agglutination of the bacteria.
5. In 1940, this substance was identified as a protein called C-reactive protein (CRP).
6. Its detection limit for infection and autoimmune diseases was 3 to 8 mg/L.

What is the mechanism of action of C-Reactive Protein (CRP)?

1. It binds the C-polysaccharide of Streptococcus pneumoniae and agglutinates the bacteria.
2. This complex CRP is a potent opsonin for monocytes, leading to phagocytosis and activating the complement system.
3. It activates the classical complement pathway.
4. It binds to polysaccharides present in many bacteria, fungi, protozoal parasites, and histones.
5. Its production is under the control of IL-1 and IL-6.

How will you discuss the Pathophysiology of C-Reactive Protein (CRP)?

1. The name C-reactive protein originates from its reaction with streptococcal capsular polysaccharides (C).
   1. CRP is the fastest-responding acute-phase protein, increasing approximately 100 times in response to infection.
   2. So this is the most sensitive indicator.
2. This increase is observed in many diseases, so it lacks specificity.
3. This is a nonspecific acute-phase protein with gamma mobility and is very helpful in monitoring inflammation.
   1. C-reactive protein on serum electrophoresis is found in the gamma region.
4. CRP is synthesized in the liver, and antigen complexes initiate its synthesis.
5. Its production is controlled by interleukin-6.
6. CRP forms complexes on the surface of bacteria (E.coli, S.pneumoniae), fungi, and other microorganisms.
7. CRP binds to polysaccharides present in many bacteria, fungi, protozoal parasites, and histones.
8. It is found in the Gamma-region band on serum electrophoresis.

What is the pattern of C-Reactive protein (CRP) in inflammation?

1. CRP is absent from a healthy person.
2. CRP  increased after any injury (trauma, bacterial infection, surgery, neoplasm, and inflammation) by 100 times.
   1. This is a nonspecific acute-phase protein.
3. CRP rises after 4 to 6 hours of the infection (within 24 hours), while other proteins rise after 12 to 36 hours of the initiating cause.
   1. The peak level is at 72 hours.
   2. C-Reactive Protein (CRP) becomes negative after 7 days.

How does the synthesis of C-Reactive Protein (CRP) take place?

1. CRP is functionally analogous to IgG, except it is not antigen-specific.
   1. This protein is synthesized in the liver and released into the bloodstream after tissue injury within a few hours.
2. The synthesisof the CRP is initiated by:
   1. Antigen immune complexes.
   2. Bacterial infection.
   3. Fungal infection.
   4. Trauma or tissue injury.

High-sensitivity CRP (hs-CRP):

How will you define High-sensitivity CRP?

1. hs-CRP is produced in the liver and is an acute-phase reactant.
   1. It is induced by the release of interleukins 1 and 6, which reflect systemic inflammation activation.
2. It detects the lower level of CRP, which is important for finding the risk of cardiac events.
3. The sensitivity is 0.01 mg/dL.
4. In cases of elevated hs-CRP, follow-up serial measurements are necessary.
5. hs-CRP is useful for the risk of developing acute myocardial infarction with a history of acute coronary syndrome.
6. Value ≥1.0 mg/L indicates subclinical infection/inflammation; the test must be repeated in 3 to 4 weeks.

What is the relation of hs-CRP for Coronary risk grades?

What is the significance of C-Reactive Protein (CRP)?

1. It is the first acute-phase protein to be raised in inflammatory diseases, and its level increases significantly.
   1. It is raised in acute and chronic inflammation.
2. This promotes the binding of Complements and helps in phagocytosis.

3. The antigen-antibody immune complex initiates the formation of C-Reactive Protein (CRP).
4. Failure of the CRP to return to normal indicates tissue damage in the heart or elsewhere.
5. The absence of CRP increase raises the question of necrosis before 2 to 10 days.
6. CRP is usually normal in unstable angina patients where there is no necrosis.
7. CRP may remain increased for at least 3 months after an Acute myocardial infarction (AMI).
   1. Peak CRP correlates with the peak of CK-MB in AMI.

8. This can induce the production of cytokines.
9. This can cause inhibition of chemotaxis and modulation of the WBC function.
10. The average CRP level is <2 to 3 mg/L.
    1. The markedly raised level of >10 mg/L indicates an active inflammatory condition, such as collagen disease and infection.
    2. Its level does not rise consistently in the virus infection.

CRP vs. ESR:

1. CRP is more sensitive and responds more rapidly than the ESR.
2. Other physiologic factors influence ESR, but CRP does not.
3. CRP tends to increase before the increase in ESR and antibody titer.
4. CRP exhibits an earlier and more rapid increase in the acute inflammatory process compared to ESR.
5. In recovery, it becomes normal before the ESR.
6. It disappears when the disease is treated with cortisone or salicylates.
7. This is useful for assessing the risk of myocardial infarction in patients with acute coronary signs and symptoms.

What is the role of C-reactive protein in various diseases?

1. CRP may be an indicator of various diseases, such as:
   1. Tissue injury or necrosis of the tissues.
   2. Various infections.
   3. Monitoring the course and effect of therapy.

What is the role of CRP in myocardial infarction (AMI)?

1. CRP is raised, and it correlates with the CK-MB isoenzyme in AMI.
2. Its peak level occurs 1 to 3 days later than CK-MB.
3. hs-CRP values >10 mg/L within 6 to 24 hours after the symptom onset indicate an increased risk for a recurrent cardiac event within 30 days to 1 year.
4. In unstable angina, hs-CRP values >10 mg/L will predict a higher chance of myocardial infarction/death than in patients with hs-CRP <10 mg/L.
5. CRP may remain increased in AMI for at least three months.
6. If the level persists, being raised indicates ongoing damage to myocardial tissue.
7. The baseline level is a reliable indicator of future cardiovascular disease risk.
   1. CRP is a stronger predictor of cardiovascular disease than low-density lipoprotein (LDL) and cholesterol.
   2. CRP is a good marker for assessing the likelihood of recurrent myocardial infarction, restenosis, or death in patients with stable coronary disease.
   3. Its raised level is also reported as a risk factor for the development of hypertension.
8. Its level is normal in the case of angina.

What is the value of CRP in Pancreatitis?

1. A level of 150 mg/L distinguishes mild from severe acute pancreatitis.

What is the value of  CRP in the rejection phenomenon?

1. It helps the rejection of kidney or bone marrow transplants but is not helpful in heart transplants.

What is the value of CRP in malignant tumors?

1. In 1/3 of the cases, CRP is >10 mg/L in malignant tumors of the breast, lungs, and GI tract.

What is the significance of CRP after surgery?

1. It may be advisable after the surgery, when the level increases in 4 to 6 hours.
2. The peak level is reached within 48 to 72 hours.
3. It starts to decline after the third postoperative day.
4. It returns to normal in 5 to 7 days.
5. Failure to return to a normal level indicates a complication of infection or pulmonary infarction.
   1. In those cases, advise CBC, ESR, temperature check, and pulse rate.

What is the significance of CRP in the case of Meningitis?

1. It helps in the differential diagnosis of bacterial or viral meningitis.
2. In viral meningitis, it will not be raised.
3. The normal value excludes bacterial meningitis.

What will be the value of CRP in burns?

1. The level may exceed 1000 mg/L.

Why is the CRP level useful in various conditions?

1. Clinical evaluation of SLE, leukemia, Blast crisis, and ulcerative colitis.
2. There is a good correlation with ESR, but CRP appears and disappears earlier than changes in ESR.
3. The level of CRP increases dramatically than other Acute-phase proteins. So CRP is more useful as an acute-phase protein.
4. The quantitative test is more useful than a qualitative test.

What are the Jones criteria for the diagnosis of Rheumatic fever?

How will you interpret the CRP serology?

1. CRP appears 24 to 48 hours after the onset of infection.
2. The peak level reaches 72 hours.
3. It disappears from circulation after seven days.

4. Based on the CRP level, there  are the following categories:
   1. Normal level = <3 mg/L.
   2. High-level CRP = >10 mg/L (active inflammation).
   3. Low-level CRP =  3 to 10 mg/L. (Cellular stress).

What are the normal C-Reactive Protein (CRP) values?

• <1.0 mg/dL
• Source 2
• <1.0 mg/dL or <10.0 mg/L
• Cardiac disease risk:
  • Low = <1.0 mg/dL
  • Average = 1.0 to 3.0 mg/dL
  • High = >3.0 mg/dL
• Source 4
  • CRP = <0.8 mg/dL (<8.0 mg/L) (by nephelometry)
  • CRP reportable value = 0.3 to 20 mg/dL
  • hs-CRP = 0.020 to 0.800 mg/dL  (0.2 to 8.0 mg/L) (by immunoassay)
• Value ≥1.0 mg/L represents subclinical infection/inflammation and should be repeated in 3 to 4 weeks.

What are the causes of raised CRP levels?

1. Soft tissue Trauma.
2. Infection.
3. Tissue necrosis.
4. Patients with Rheumatoid arthritis.
5. In Rheumatic fever.
6. Patients with systemic lupus erythematosus.
7. Patient with pneumonia.
8. Patient with malignancies.
9. In pregnant ladies.
10. Pulmonary tuberculosis.
11. Urinary tract infection.
12. Myocardial infarction.
13. Vasculitis syndrome.
14. Bacterial meningitis.

What are the causes of decreased CRP levels?

1. This may be seen in the moderate use of alcohol.
2. In weight loss.
3. Strenuous exercise.
4. Medicine like Niacin and statin.
5. Pregnancy.
6. Angina.
7. Seizures.
8. Asthma.
9. Common cold.
10. Rejection of heart transplant.
11. Autoimmune diseases like SLE, scleroderma, dermatomyositis, and mixed connective tissue disease.

What is the panic value of hs-CRP?

• >3.5 mg/L
• In acute inflammation = >10.0 mg/L

Questions and answers: