Standardization of immunoassays for measurement of high-sensitivity C-reactive protein. Phase I: evaluation of secondary reference materials.
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.
Kimberly
Mary M
MM
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341-3724, USA. mkimberly@cdc.gov
Vesper
Hubert W
HW
Caudill
Samuel P
SP
Cooper
Gerald R
GR
Rifai
Nader
N
Dati
Francesco
F
Myers
Gary L
GL
D002097:C-Reactive Protein / Q000032:analysis / Q000592:standards*; D006801:Humans; D007118:Immunoassay / Q000379:methods / Q000592:standards; D017270:Lipoprotein(a) / Q000032:analysis / Q000592:standards; D008163:Luminescent Measurements; D009211:Myoglobin / Q000032:analysis / Q000592:standards; D009391:Nephelometry and Turbidimetry / Q000379:methods / Q000592:standards; D011994:Recombinant Proteins / Q000592:standards; D012015:Reference Standards
D017270:Lipoprotein(a); D009211:Myoglobin; D011994:Recombinant Proteins; D002097:C-Reactive Protein