Characterization of the New Serum Protein Reference Material ERM-DA470k/IFCC: Value Assignment by Immunoassay

Abstract

BACKGROUND The availability of a suitable matrix reference material is essential for standardization of the immunoassays used to measure serum proteins. The earlier serum protein reference material ERM-DA470 (previously called CRM470), certified in 1993, has led to a high degree of harmonization of the measurement results. A new serum protein material has now been prepared and its suitability in term of homogeneity and stability has been verified; after characterization, the material has been certified as ERM-DA470k/IFCC. METHODS We characterized the candidate reference material for 14 proteins by applying a protocol that is considered to be a reference measurement procedure, by use of optimized immunoassays. ERM-DA470 was used as a calibrant. RESULTS For 12 proteins [α2 macroglobulin (A2M), α1 acid glycoprotein (orosomucoid, AAG), α1 antitrypsin (α1-protease inhibitor, AAT), albumin (ALB), complement 3c (C3c), complement 4 (C4), haptoglobin (HPT), IgA, IgG, IgM, transferrin (TRF), and transthyretin (TTR)], the results allowed assignment of certified values in ERM-DA470k/IFCC. For CRP, we observed a bias between the lyophilized and liquid frozen materials, and for CER, the distribution of values was too broad. Therefore, these 2 proteins were not certified in the ERM-DA470k/IFCC. Different value transfer procedures were tested (open and closed procedures) and found to provide equivalent results. CONCLUSIONS A new serum protein reference material has been produced, and values have been successfully assigned for 12 proteins.

Harmonization in laboratory medicine: the complete picture

“…The availability of a suitable matrix reference material for the measurement of serum protein (ERM-DA470, previously called CRM470) has led to a high level of harmonization in measurement results for 15 human serum proteins [ 29 ]. More recently, a new serum protein reference material (ERM-DA470k/IFCC) has been produced to replace ERM-DA470, and values have been successfully assigned to 12 proteins [ 30 ].…”

Quantitative Measurement of Immunoglobulins and Free Light Chains Using Mass Spectrometry

“…29 The sensitivity of the SRM method was assessed by titrating purified human κ and λ free light chains (Bethyl Laboratories, Montgomery, TX) in a serum matrix from an aplastic phase following stem cell transplantation, low in endogenous immunoglobulins.…”

A reference system for urinary albumin: current status

“…In 2008 this batch of material was exhausted and ERM-DA470k/IFCC was released to replace it. The value for albumin in ERM-DA40k/IFCC was again assigned by immunoassays, using ERM-DA470 as calibrator [ 2 ].…”

“…Considerable inter-method differences have been reported for both albumin and creatinine measurement procedures [and, therefore, the albumin-to-creatinine ratio (ACR)], but accuracy is unknown and there are no independent reference measurement procedures for albumin and no reference materials for either measurand in urine [ 1 ]. At present most IVD manufacturers provide calibrators with values that are traceable either to the serum reference material ERM-DA470k/IFCC, certified for its albumin content by immunoassay [ 2 ], or to purified albumin preparations. Only recently a highly purified human serum albumin reference material was prepared specifically for the standardization of urinary albumin measurements [ 3 ].…”