High sensitivity C-Reactive Protein (CRP)
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High sensitivity C-Reactive Protein (CRP)


by Harris Ramuth, Dip MLT (University of Mauritius)
Email: hybrid2002@servihoo.com
C-Reactive protein (CRP) is a pentameric acute phase reactant that is synthesized by the liver. Its production is controlled primarily by interleukin-6 (IL-6). The serum CRP concentration may increase by up to 1000-fold with infection, trauma, surgery, and other acute inflammatory events. Chronic inflammatory disorders, including autoimmune diseases and malignancy, can produce persistent increases of serum CRP concentrations.


Traditionally, CRP has been used clinically for diagnosis and monitoring of autoimmune and infectious disorders. The diagnosis of early infection (< 48 hours) particularly in the absence of signs and symptoms is very difficult and intricate and this is even more so in neonate infections.


Early-onset sepsis in neonates can for example be satisfactorily detected and treated. The use of serial CRP measurements in such cases can be of great help. The cascade of inflammation starts and CRP levels can be best detected 24 hour and 48 hour after infection is suspected .However, there are reports of elevated non specific CRP levels 2-3 days after birth which can considerably reduce the positive predictive value of CRP estimations (Jaye DL ,1997).

 
The  prerequisite, however ,for analyzing the CRP responses associated with infectious and non infectious conditions during the immediate postnatal period is the need to establish the "normal" dynamics of  both variables in the healthy neonate, counterbalanced by a greater awareness of the maternal and perinatal factors that may affect them. CRP has also proved to be an excellent marker for future cardiac problems and has a good prognostic factor concerning the disease (Kuller LH et al, 1996). As already stated previously, CRP is a marker of inflammation in general. This inflammation  leads to the formation of plaques with the involvement of monocytes and  eventually cause cardio vascular complications. Routine automated methods for CRP quantification in the clinical laboratory typically have limits of quantification of 3?8 mg/L. However, the lower limit that is required as a marker of traditional inflammation is 10 times lower for predicting cardiac complications (Ridker PM et al, 1998).High sensitivity CRP assays evaluated together with common risk factors by a cardiac panel can better evaluate future risk of complications than traditional cardiac markers. The within-person biologic variability of hs-CRP is also low over a long period of
time.

These hs-CRP cutpoints have been  established in prospective epidemiologic studies .Hence, the need for devising new techniques to detect these high sensitivity CRP.A latex-enhanced immunonephelometric hs-CRP method has been reported as well as several automated immunoturbidimetric and immunoluminometric hs-CRP assays to satisfactorily satisfy the criteria of sensitivity and precision at low levels of concentration ( Roberts WL et al,2000).

An analytical  detection limit  of  0.00016 mg/L has been reported in immuno assay techniques correlating well with established assays such as the Dade Behring N High Sensitivity CRP assay (Piia Tarkkinen et al, 2002).  Other methods for evaluating high sensitivity CRP include methods from  Daiichi, Denka Seiken, Diagnostic Products Corporation, Iatron, Kamiya, Olympus, Roche, and Wako. The Dade Behring BN II, the Abbott IMx, the Diagnostic Products Corporation IMMULITE, and the Beckman Coulter IMMAGE are four automated analyzers with high-sensitivity CRP (hs-CRP) methods. hs-CRP has a degree of measurement stability that is similar to that of total cholesterol(Ira S. Ockene et al,2001)

A study involving 9 high sensitivity CRP detection methods has revealed that prozone affects the results in some cases.The study has also emphasised the need for a proper standardisation of procedures (William L. Roberts et al,2001). CRM470  is a reference material for the acute-phase reactant range, which  will probably be  used in the phase to standardize hsCRP assays.


Conclusion :


hsCRP has a bright future in pathology as a marker of cardiovascular disease especially if it is associated with  other common risk factors such as high cholesterol , obesity ,smoking habits etc. Proper standardization of the method is mandatory and elaborate protocols which will eliminate errors like those due to prozone effect must be encouraged .Early detection of an abnormal rise in the level of CRP can then  be effectively  used to prevent further complications.

References

Ira S. Ockene, Charles E. Matthews, Nader Rifai, Paul M. Ridker, George Reed and Edward Stanek.( 2001) Variability and Classification Accuracy of Serial High-Sensitivity C-Reactive Protein Measurements in Healthy Adults. Clin Chem. 47 p444-450.


Jaye DL and  Waites KB.( 1997). Clinical applications of C-reactive protein in pediatrics. Pediatr Infect Dis J. 16 p735-747.

Kuller LH, Tracy RP, Shaten J and Meilahn EN.(1996). Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple Risk Factor Intervention Trial. Am J Epidemiol. 144 p537-547.


Piia Tarkkinen, Tom Palenius and Timo Lövgren (2002). Ultrarapid, Ultrasensitive One-Step Kinetic Immunoassay for C-Reactive Protein (CRP) in Whole Blood Samples: Measurement of the Entire CRP Concentration Range with a Single Sample Dilution. Clin Chem. 48 p269-277.

Ridker PM, Cushman M, Stampfer MJ, Tracy RP and Hennekens CH. (1998)  Plasma concentration C-reactive protein and risk of developing peripheral vascular disease. Circulation.  97 p425-428



Roberts WL, Sedrick R, Moulton L, Spencer A  and Rifai N. (2000) Evaluation of four automated high sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Clin Chem.;46 p461-468

William L. Roberts, Linda Moulton, Terence C. Law, Genesis Farrow, Margaret Cooper-Anderson, John Savory and Nader Rifai. (2001) Evaluation of Nine Automated High-Sensitivity C-Reactive Protein Methods: Implications for clinical and epidemiological applications .Clin Chem. 47 p418-425

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