Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach - PubMed (original) (raw)

Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach

Alain Van Dorsselaer et al. PLoS One. 2011.

Abstract

Background: Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG).

Methodology/principal findings: Using a classical proteomic approach, 33 and 34 non-gonadotropin proteins were identified in urinary human chorionic gonadotropin (u-hCG) and highly-purified urinary human menopausal gonadotropin (hMG-HP) products, respectively. Prion protein was identified as a major contaminant in u-hCG preparations for the first time. An advanced prion protein targeted proteomic approach was subsequently used to conduct a survey of gonadotropin products; this approach detected human prion protein peptides in urine-derived injectable fertility products containing hCG, hMG and hMG-HP, but not in recombinant products.

Conclusions/significance: The presence of protease-sensitive prion protein in urinary-derived injectable fertility products containing hCG, hMG, and hMG-HP suggests that prions may co-purify in these products. Intramuscular injection is a relatively efficient route of transmission of human prion disease, and young women exposed to prions can be expected to survive an incubation period associated with a minimal inoculum. The risks of urine-derived fertility products could now outweigh their benefits, particularly considering the availability of recombinant products.

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Conflict of interest statement

Competing Interests: Dr. McNair is Vice-President of Cerner Corporation, which had no role in the initiation or conduct of this study. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1

Figure 1. 2D gel electrophoresis separation of urinary and recombinant hCG products (6,500 IU loaded).

(A) u-hCG manufacturer A. (B) u-hCG Manufacturer B. (C) r-hCG Manufacturer D. (D) Zoom views on the regions of gels (A) and (B) with spots containing PrP peptides encircled.

Figure 2

Figure 2. Human prion protein (PrP) sequence (mature form in bold).

*Tryptic peptides identified in human chorionic gonadotropin (hCG) preparations (PrP 121-136, PrP 137-148, PrP 157-164, PrP 209-220, and PrP 221-228) are underlined.

Figure 3

Figure 3. 2D gel electrophoresis separation of urinary hMG and recombinant hFSH/hLH products.

(A) hMG Manufacturer A (600 IU loaded). (B) hMG Manufacturer C (1,125 IU loaded). (C) r-hFSH/r-hLH Manufacturer D (1,125 IU loaded).

Figure 4

Figure 4. 2D gel electrophoresis separation of highly purified urinary hMG and recombinant hFSH/hLH products (1,125 IU loaded).

(A) hMG-HP Manufacturer A-Product 1. (B) hMG-HP Manufacturer A-Product 2. (C) r-hFSH/r-hLH Manufacturer D.

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