C-Reactive Protein (CRP), High-Sensitivity C-Reactive Protein (hs-CRP), Acute Phase Protein

Acute-phase protein (Acute Phase Reactants)

• Acute-phase proteins are raised in inflammatory conditions.
• When there is an increase in an acute phase protein called positive acute-phase protein.
  • In the case of a decrease in the acute phase protein, it is called negative phase protein.
• 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)

Sample

1. The venous blood of the patient 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 can store at 4 °C for <72 hours.
   2. At -20 °C for six months.

Indications

1. Advised in bacterial infection.
2. It is advised in rheumatic fever.
3. It is advised in rheumatoid arthritis.
4. It may be advised after the surgery.

Precautions

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 have seen weight loss, moderate consumption of alcohol, and exercise.
5. Estrogens and progesterone increase value.
6. Niacin, statin, and fibrates decrease value.

Pathophysiology

1. Definition:
   1. CRP is produced in the liver, and its name is derived from its reaction with streptococcal capsular polysaccharides.
   2. CRP level supporting bacterial endocarditis, appendicitis, and active collagen diseases was >10 mg/L.
      

      CRP synthesis and its reaction with streptococcal capsule polysaccharide

2. 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.
3. The acute reaction proteins  pattern is also called:
   1. Acute inflammatory response pattern.
   2. Acute stress pattern.
   3. Acute-phase protein pattern.
4. CRP is found in the Gamma-region band on serum electrophoresis.
   

   CRP on electrophoresis

5. CRP is absent from the healthy person.
6. CRP  increased after any injury (trauma, bacterial infection, surgery, neoplasm, and inflammation) to 100 times.
7. CRP  was given the name in 1941 that it is protein.
   1. This is a nonspecific acute-phase protein.
   2. CRP starts rising after 4 to 6 hours of the infection, while other proteins rise after 12 to 36 hours of the initiating cause.
   3. CRP is functionally analogous to IgG, except it is not antigen-specific.
   4. This protein is synthesized in the liver and released into blood circulation after tissue injury in a few hours.
      1. The synthesis of the CRP is initiated by:
         1. Antigen immune complexes.
         2. Bacterial infection.
         3. Fungal infection.
         4. Trauma or tissue injury.
8. High-sensitivity CRP (hs-CRP):
   1. It detects the lower level of CRP, which is important to find the risk of cardiac events.
   2. The sensitivity is 0.01 mg/dL.
   3. In the case of raised hs-CRP, follow-up serial measurements are needed.
   4. hs-CRP is useful for the risk of developing acute myocardial infarction with a history of the acute coronary syndrome.
   5. Value ≥1.0 mg/L indicates subclinical infection/inflammation; this needs to repeat the test in 3 to 4 weeks.
   6. Coronary risk grades:
      1. Low-risk = <1.0 mg/L
      2. Average risk = 1.0 to 3.0 mg/L.
      3. High-risk = ≥3.0 mg/L.
9. It is the first acute phase protein raised in inflammatory diseases, and its level increases tremendously.
   1. It is raised in acute and chronic inflammation.
10. This promotes the binding of Complement and helps in phagocytosis.
    

    CRP and complement activation

11. Its formation is initiated by the antigen-antibody immune complex.
    

    CRP and complement activation

11. This can induce the production of cytokines.
12. This can cause inhibition of chemotaxis and modulation of the WBC function.
13. The normal CRP level is <2 to 3 mg/L.
    1. The markedly raised level of >10 mg/L indicates an active inflammatory condition like collagen diseases and infection.
    2. Its level does not rise consistently in the virus infection.
14. CRP vs. ESR:
    1. More sensitive and rapidly responding than the ESR.
    2. Other physiologic factors influence ESR, but CRP does not.
    3. CRP tends to increase before the increase in ESR and the rise in antibodies titer.
    4. In the acute inflammatory process, CRP shows an earlier and more rapid increase than the 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 the assessment of risk for developing myocardial infarction in patients presenting with acute coronary signs and symptoms.
15. It may be advised after the surgery when its level increases in 4 to 6 hours.
    1. It starts going down after a 3rd postoperative day.
    2. If it persists raised level which indicates a complication of infection or pulmonary infarction.
16. It helps in the differential diagnosis of bacterial or viral meningitis.
    1. In viral meningitis, it will not be raised.
    2. Normal value excludes bacterial meningitis.
17. In myocardial infarction (AMI):
    1. CRP is raised, and it correlates with 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 indicates 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 as compared to the group of patients where hs-CRP <10 mg/L.
    5. CRP may remain increased in AMI for at least three months.
    6. If the level persists to be raised indicates ongoing damage to myocardial tissue.
    7. The baseline level is a good marker for future cardiovascular disease.
       1. CRP is a strong predictor of cardiovascular diseases than the low-density-lipoprotein (LDL) and cholesterol.
       2. In patients with stable coronary disease, CRP is a good marker for assessing the likelihood of recurrent myocardial infarction, restenosis, or death.
    8. Its level is normal in the case of angina.
18. Serology of CRP:
    1. CRP appears after 24 to 48 hours of the onset of infection.
    2. Peak level reaches 72 hours.
    3. It disappears from circulation after seven days.

1. Based upon 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).

Normal

• <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 repotable value = 0.3 to 20 mg/dL
  • hs-CRP = 0.020 to 0.800 mg/dL  (o.2 to 8.0 mg/L) (by immunoassay)

The raised level is seen in:

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

Decreased CRP level is seen in:

1. This may be seen in the moderate use of alcohol.
2. In weight loss.
3. Excessive exercise.
4. Medicine like Niacin, and a statin.

---