Severe experimental folate deficiency in a human subject - a longitudinal investigation of red-cell folate immunoassay errors as megaloblastic anaemia develops
http://www.springerplus.com/content/3/1/441

Abstract

Background

The few published studies comparing results between commercial red-cell folate immunoassays have found significant differences. None have provided longitudinal data during  the  development  of  megaloblastic  anaemia  from  severe  folate  deficiency.  The objective was to produce longitudinal data, comparing results between three commercial immunoassays for red-cell folate, generated by means of severe experimental folate deficiency.

Methods

This 58 year old male, initially replete in folate, used a folate-deficient diet to severely deplete himself of folate until overt megaloblastic anaemia developed. The Siemens Advia Centaur, Roche Elecsys 2010 and Beckman UniCel DxI 800 Access immunoassay systems were used, by different clinical pathology laboratories, to perform weekly assays for red-cell folate throughout the depletion stage. The results were analysed graphically four ways: comparison  with  lines of equality;  number of  standard deviations  difference against  the means; number of standard deviations difference over time; variation over time.

Results

There were very significant differences, varying with time and folate concentration, between the results reported by the three laboratories. The differences were greatest, up to 17 standard deviations, between the Siemens Advia Centaur and each of the other two systems. Of the 85 results comparing the Siemens Advia Centaur and the Roche Elecsys 2010, two were within the 99.9% confidence interval. Of the 91 results comparing the Siemens Advia Centaur and the Beckman UniCel DxI 800 Access, 22 were within the 99.9% confidence interval. Of the
83 results comparing the Beckman UniCel DxI 800 Access and the Roche Elecsys 2010, 37 were within the 99.9% confidence interval.

Conclusions

Comparative longitudinal data from clinical pathology laboratories, produced during experimental folate deficiency, have exposed very significant differences in results between commercial red-cell folate immunoassays. One immunoassay, the Roche Elecsys 2010, failed to detect overt megaloblastic anaemia of severe folate deficiency.

Keywords

Red-cell folate immunoassays; Immunoassay errors; Megaloblastic anaemia; Diagnosis of folate deficiency