Inadequate attempts to measure the microheterogeneity of transthyretin by low-resolution mass spectrometry

Recently, the authors of 2 studies have claimed to measure accurately the microheterogeneity of transthyretin (TTR) variants by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) immunoassays (1)(2). Here we report that the mass spectrometric performance in those studies was not adequate to measure the respective TTR variants. A mass resolution of at least 1000 is required to separate the majority of the currently known posttranslational and mutation-based modifications of TTR (3). Wang et al.(1) performed their analysis at a resolution of 270 [estimated as follows: m /Δ m FWHM = 13828/52 = 266 in Fig. 1A of their report (1)], whereas Schweigert et al. (2) achieved a resolution of 90 [estimated as follows: m /Δ m FWHM = 13851/158 = 88 in panel A2 of Fig. 2 of their report (2)]. We therefore question whether these studies can justify their reported claims. To provide arguments, we performed MALDI-TOF MS analysis on a gold chip ProteinChip® array of a commercially available TTR preparation with an instrument typically used in SELDI-TOF MS (PBS IIc analyzer; Ciphergen). We applied …