Key result
Assays calibrated against the WHO IRR 87/518 standard, which has low purity (44%) and incorrectly assigned protein content, report total IGF-I concentrations in excess of actual values.
Assays calibrated against WHO IRR 87/518 report falsely elevated total IGF-I concentrations due to the low purity and inaccurate protein content assignment of the reference standard.
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May overestimate IGF-I and mislead clinical interpretation; leaves open need for revised assay standards in research.
There is a significant systematic difference between the normal range obtained from ethylenediamine tetraacetate plasma samples using the Genentech total insulin-like growth factor I (IGF-I) RIA and normal ranges for other total IGF-I RIAs. To determine whether the quality of the assay standard was the cause of this systematic difference, we analyzed commercially available preparations of recombinant human IGF-I (rhIGF-I) typical of those used as IGF-I immunoassay standards along with our own well characterized rhIGF-I assay standard. For the commercial standards, high performance liquid chromatography-derived purities were low, and some vendor-assigned protein concentrations were inconsistent with values from quantitative amino acid analysis. The Genentech rhIGF-I assay standard was highly pure and quantitatively correct. However, the poor quality of some commercial rhIGF-I preparations was not the primary reason for the systematic discrepancy between the Genentech total IGF-I RIA normal range and most other normal ranges. Most assays for total IGF-I are calibrated against the WHO International Reference Reagent (IRR) for IGF-I Immunoassays (87/518). The Genentech total IGF-I RIA is not calibrated against WHO IRR 87/518. The protein content assigned to WHO IRR 87/518 was a consensus value from a multicenter collaborative study. Physico-chemical analyses showed that WHO IRR 87/518 is Met−1-IGF-I of low purity (44%), and that the assigned protein content is higher than the value determined by quantitative amino acid analysis. Thus, assays that are calibrated against WHO IRR 87/518 will report total IGF-I concentrations in excess of actual values. We believe that calibration against WHO IRR 87/518 is the cause of the systematic discrepancy between the Genentech IGF-I assay normal range and most other normal ranges, and that much of the plasma IGF-I concentration data in the literature are of questionable accuracy.
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Valerie Quarmby (1998) studied IGF-I assay accuracy. Genentech total IGF-I RIA and assay standard vs. WHO International Reference Reagent (IRR) 87/518 and commercial standards was evaluated on Purity and protein content of IGF-I assay standards. Assays calibrated against the WHO IRR 87/518 standard, which has low purity (44%) and incorrectly assigned protein content, report total IGF-I concentrations in excess of actual values.
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