title: Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.
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).
  
  
  RESULTS
  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
  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.
authors: Laboratoire de Spectrométrie de Masse Bio-Organique, Université de Strasbourg, IPHC, CNRS, UMR7178, Strasbourg, France. vandors@unistra.fr
authors: Alain
authors: A
authors: Van Dorsselaer
authors: Christine
authors: C
authors: Carapito
authors: François
authors: F
authors: Delalande
authors: Christine
authors: C
authors: Schaeffer-Reiss
authors: Daniele
authors: D
authors: Thierse
authors: Hélène
authors: H
authors: Diemer
authors: Douglas S
authors: DS
authors: McNair
authors: Daniel
authors: D
authors: Krewski
authors: Neil R
authors: NR
authors: Cashman
mesh_terms: D000595:Amino Acid Sequence; D006063:Chorionic Gonadotropin / Q000652:urine; D002853:Chromatography, Liquid; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005299:Fertility Agents / Q000652:urine*; D006801:Humans; D007267:Injections; D013058:Mass Spectrometry; D008596:Menotropins / Q000302:isolation & purification / Q000652:urine; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011328:Prions / Q000737:chemistry / Q000652:urine*; D040901:Proteomics / Q000379:methods*; D012015:Reference Standards
chemical_list: D006063:Chorionic Gonadotropin; D005299:Fertility Agents; D010455:Peptides; D011328:Prions; D008596:Menotropins