title: A non-invasive method based on saliva to characterize transthyretin in familial amyloidotic polyneuropathy patients using FT-ICR high-resolution MS.
abstract: OBJECTIVE
  To identify, characterize and perform a relative quantification of human transthyretin (TTR) variants in human saliva.
  
  
  METHODS
  Serum and saliva samples were collected from healthy and familial amyloidotic polyneuropathy (FAP) patients, proteins separated by SDS-PAGE, TTR bands excised, in-gel digested and analyzed by MALDI-FTICR.
  
  
  RESULTS
  We identified and performed a relative quantification of mutated and native TTR forms in human saliva, based on FTICR-MS. The results are quantitatively identical to the ones obtained with human serum. In FAP patients subjected to cadaveric liver transplant, the TTR mutant form is no longer detected in saliva, while in patients receiving a domino liver from a FAP donor the mutant form of TTR becomes detectable in saliva, thus demonstrating the serum origin of TTR in saliva.
  
  
  CONCLUSIONS
  Saliva TTR originates in serum and the ratio of mutant to native TTR is preserved. The method provides a non-invasive detection of mutated TTR and a relative quantification of TTR forms. Diagnostic and disease prognosis of FAP is crucial at early stages of the disease and after liver transplantation, the only curative therapy. A suitable non-invasive method was developed for monitoring the most important FAP biomarker in human saliva.
authors.affiliation: Departamento de Química e Bioquímica, Centro de Química e Bioquímica, Faculdade de Ciências da Universidadede Lisboa, Edifício C8, Lisboa, Portugal.
authors.forename: Gonçalo
authors.initials: G
authors.lastname: da Costa
authors.forename: Ana
authors.initials: A
authors.lastname: Guerreiro
authors.forename: Catarina F
authors.initials: CF
authors.lastname: Correia
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Gomes
authors.forename: António
authors.initials: A
authors.lastname: Freire
authors.forename: Estela
authors.initials: E
authors.lastname: Monteiro
authors.forename: Eduardo
authors.initials: E
authors.lastname: Barroso
authors.forename: Ana V
authors.initials: AV
authors.lastname: Coelho
authors.forename: Tiago F
authors.initials: TF
authors.lastname: Outeiro
authors.forename: Ana Ponces
authors.initials: AP
authors.lastname: Freire
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordeiro
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000097:blood / Q000235:genetics*; D006801:Humans; D011228:Prealbumin / Q000032:analysis / Q000235:genetics*; D012463:Saliva / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D011228:Prealbumin