CRP C- reactive protein

C- reactive protein (CRP) C-reactive protein was originally discovered as a substance in the serum of patients with acute inflammation that react with the C polysaccharide of pneumococcus, this protein which cause the reaction is called CRP. It is an acute phase protein which act as a non specific inflammatory indicator.

Characteristics of CRP CRP is alpha-globulin produced in liver. CRP is acute phase protein that appears in sera of individuals in response to inflammatory conditions (e.g. rheumatoid arthritis and lupus …,etc.) and some forms of cancer. Increase within 4-6 hours following infection, surgery or trauma. CRP also elevated due to inflammation in the arteries of the heart and is a marker for coronary artery disease called high sensitive CRP(hs- CRP).

CRP is not specific. A high result serves as a general indication of acute inflammation but can’t show where the inflammation is located or what is causing it so, Other tests are needed to find the cause and location of the inflammation. It is thermolabile destroyed by heating at 70◦ C for 30 min. Don’t cross human placenta. Act as opsonin to help in complement activation and has a receptor on phagocytic cells.

CRP pathophysiology

CRP and coronary heart disease Hs CRP appears within one to two days of acute myocardial infarction, peaks at 3 days and becomes negative after seven days  Failure of CRP to return to normal signifies tissue damage in the cardiac or other tissues. Hs CRP correlates with peak CKMB following acute myocardial infarction. CRP may remain high for at least three months following acute myocardial infarction.

When it is ordered? Suspected inflammatory state (vasculitis, autoimmune disorders, SLE, infection) May sometimes be ordered along with erythrocyte sedimentation rate (ESR) hs-CRP can be ordered for patients with some established risk factors of coronary heart disease to determine strategy for prevention of cardiovascular events and for follow-up of patients with acute coronary syndromes.

When it is ordered? CRP 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. CRP may also be ordered to monitor conditions such as rheumatoid arthritis and lupus and is often repeated at intervals to determine effectiveness of treatment.

When it is ordered? Check for infection after surgery. CRP level normally rise within 4-6 hr of surgery and then go down by the third day after surgery. If CRP level stay elevated after 3 days of surgery, an infection may be present. Check to see how well treatment is working, such as treatment for cancer or an infection. CRP level rise rapidly with infection but quickly become normal if you are responding to treatment.

CRP vs ESR Both are indicators for non specific inflammation, but CRP is a more sensitive and accurate reflection of the acute phase response than the ESR, since ESR may be normal while CRP is elevated But.. CRP appears and disappears more quickly than changes in ESR. Therefore, your CRP level may drop to normal following successful treatment, whereas ESR remain elevated for a longer period. The CRP methods used in the laboratory are a more direct measure of the inflammatory process, because only CRP is measured, by contrast ESR is a more indirect measure. ESR reflects the concentration of several plasma proteins including fibrinogen, α-globulins, β-globulins, immunoglobulins and albumin. Therefore, any condition (pathological or non-pathological) that affects any of the contributing proteins can alter the ESR Both CRP and ESR have characteristic patterns of response (Figure 1). CRP begins to rise within 4-6 hours of stimulus, peaks within 48 hours, and returns to normal 3-7 days following resolution. ESR shows a much slower response, taking up to a week to peak, and up to several weeks to return to normal Days post stimulation

Conditions in which CRP is normal whereas ESR is increased: Pregnancy due to increase in fibrinogen. Nephrosis in which hypoalbuminemia present but fibrinogen and globulins increased. Anemia. Drugs (steroids). CRP versus ESR measurement Erythrocyte sedimentation rate (ESR) is more commonly used as a non-specific marker of disease activity. However, as more is learned about CRP, measuring this parameter could be a better test than the ESR. The ESR, which is an indirect parameter of acute phase protein changes, can be influenced by concentrations of fibrinogen, monoclonal proteins and red cell morphology, whereas CRP has no cross-interfaces. CRP is useful for its negative predictive value as a negative CRP rules out the possibility of an inflammatory or necrotic course. A positive reaction is certainly an indication of a problem, but it is not specific for any single disease. ESR has several disadvantages that prevent it from being an ideal laboratory test to monitor acute inflammation or tissue injury. However, the ESR remains useful for the detection of paraproteinaemia, which do not necessarily provoke an acute phase response. SLE and progressive systemic sclerosis, even when active, usually cause only a trivial increase in CRP (in the range 1-6 mg%), although the ESR may be very high .The reason for the discrepancy between ESR and CRP is unknown, but indicates the two tests are complementary

Normal value: 0.02-1.32 mgldl CRP Test :- 1 drop of reagent is mixed with 50ul of sample. If positive: serial dilution is done to detect the titer. If negative: serial dilution is done to exclude probability of very high concentration of CRP “prozone effect” Titer is detected by multiplying dilution factor by 0.6 mg/dl or 6 mg/L.

1 2 3 Total Dilution Add 50ul 50ul 50ul 50ul 50ul 50ul And so on; NS sample And so on; NS NS NS 1:2 1:4 1:8 Total Dilution agglutination - - + - + + Titer (mg/L) = 12 6 24 48