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