Variant transthyretin (TTR) amyloidosis in Argentina. Detection of the trait by electrospray ionization mass spectrometry of lyophilized TTR immunoprecipitate

Abstract

We have developed a quick and reliable diagnostic method for detecting variant forms of transthyretin (TTR); namely, centrifugal concentration followed by electrospray ionization mass spectrometry (ESI-MS). Argentinian patients from three families with neuropathic amyloidosis and their relatives were screened for mutated TTR by ESI-MS. In order to facilitate transportation, we investigated the impact storage had on lyophilized anti­TTR-antibody precipitates' mass spectra. For this investigation, plasma samples from three Swedish patients with known TTR amyloidosis were analysed. We detected identical, additional peaks corresponding to a variant form of TTR in 10 members of the families, and also in a lyophilized sample sent unfrozen by mail from Argentina. All except one symptomatic subject had additional peaks, the exception having undergone a liver transplantation for the disease. All patients were early onset cases, i.e. below 35 years of age, and family history suggests an aggressive, rapidly progressing disease. Lyophilized anti-TTR-antibody precipitates stored at room temperature for 1 week exhibited only minor differences compared with plasma samples stored at -70°C. In a new Argentinian study on familial amyloidotic polyneuropathy, the variant TTR was quickly identified and typed by ESI-MS. To facilitate transportation, dry­frozen samples can be used and the quality of the spectra is similar to that of samples stored at -70°C.