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A non‐invasive method based on saliva to characterize transthyretin in familial amyloidotic polyneuropathy patients using FT‐ICR high‐resolution MS
Author(s) -
da Costa Gonçalo,
Guerreiro Ana,
Correia Catarina F.,
Gomes Ricardo J.,
Freire António,
Monteiro Estela,
Barroso Eduardo,
Coelho Ana V.,
Outeiro Tiago F.,
Freire Ana Ponces,
Cordeiro Carlos
Publication year - 2010
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200900118
Subject(s) - transthyretin , saliva , polyneuropathy , amyloidosis , biomarker , medicine , liver transplantation , gastroenterology , pathology , chemistry , transplantation , biochemistry
Purpose : To identify, characterize and perform a relative quantification of human transthyretin (TTR) variants in human saliva. Experimental design : 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 and clinical relevance : 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.