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Standardization of immunoassays for measurement of high-sensitivity C-reactive protein. Phase I: evaluation of
Mary M Kimberly1, Hubert W Vesper, Samuel P Caudill
1Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341-3724, USA. mkimberly@cdc.gov
Insights
Standardizing high-sensitivity C-reactive protein (hsCRP) assays is crucial for accurate cardiovascular disease risk assessment. Certified Reference Material 470 (CRM470) demonstrated suitable characteristics for use in the next phase of hsCRP assay standardization.
Area of Science:
- Clinical Chemistry
- Biomarker Standardization
- Cardiovascular Disease Research
Background:
- Inflammation is a key factor in atherosclerosis development and progression.
- C-reactive protein (CRP) serves as a marker for cardiovascular disease (CVD) risk.
- Variability in high-sensitivity CRP (hsCRP) assays can lead to patient misclassification and hinder clinical decision-making, necessitating assay standardization.
Purpose of the Study:
- To evaluate proposed secondary reference materials for standardizing high-sensitivity CRP (hsCRP) assays.
- To assess the suitability of different reference materials for inter-assay comparisons and standardization efforts.
Main Methods:
- Five secondary reference materials were evaluated, including dilutions of Certified Reference Material 470 (CRM470) and serum-based materials with added CRP.
- Twenty-one manufacturers participated, comparing 28 different hsCRP assays.
- Imprecision, linearity, and parallelism were assessed using the reference materials and fresh serum.
Main Results:
- All evaluated materials exhibited similar imprecision (CVs 2.1-3.7%).
- No single material demonstrated linearity across all tested assays; nonlinearity was observed in some cases.
- While parallelism varied across assays, differences in slope relative to fresh serum were consistent.
Conclusions:
- The evaluated reference materials performed comparably in terms of imprecision, linearity, and parallelism.
- One preparation of CRM470 showed slightly superior characteristics and will be utilized in the subsequent phase of hsCRP assay standardization.
- CRM470's prior certification as a reference material for acute-phase reactants supports its use in standardizing hsCRP assays.
Background:
Inflammation contributes to the development and progression of atherosclerosis, and C-reactive protein (CRP) can be used as a marker to assess risk for cardiovascular diseases. As variability among existing high-sensitivity CRP (hsCRP) assays can lead to misclassification of patients and hamper implementation of population-based medical decision points, standardization of hsCRP assays is needed.
Methods:
We evaluated five proposed secondary reference materials, including two diluted preparations of Certified Reference Material 470 (CRM470), two preparations of a serum-based material with recombinant CRP added, and one serum-based material with isolated CRP added. Twenty-one manufacturers participated in the comparison with 28 different assays. We examined imprecision, linearity, and parallelism with these materials and with fresh serum.
Results:
All materials had similar imprecision; CVs for the undiluted materials were 2.1-3.7%. None of the materials was linear across all assays. Each had between one and three cases of nonlinearity, with one preparation of CRM470 having the fewest cases of nonlinearity. Although none of the materials was parallel across all assays, the differences in slope from fresh serum were similar across all assays.
Conclusions:
All materials performed similarly with regard to imprecision, linearity, and parallelism. As one preparation of CRM470 had slightly better characteristics than the other materials and because CRM470 had been certified previously as a reference material for the acute-phase reactant range, it will be used in the next phase to standardize hsCRP assays.
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