SELDI-TOF Mass Spectrometry Evaluation of Variant Transthyretins for Diagnosis and Pathogenesis of Familial Amyloidotic Polyneuropathy

Ueda, Mitsuharu; Misumi, Yohei; Mizuguchi, Mineyuki; Nakamura, Masaaki; Yamashita, Taro; Sekijima, Yoshiki; Ota, Kazutoshi; Shinriki, Satoru; Jono, Hirofumi; Ikeda, Shu Ichi; Suhr, Ole B.; Ando, Yumiko

doi:10.1373/clinchem.2008.118505

Cited by 56 publications

(33 citation statements)

References 18 publications

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“…To detect wild-type and mutant transthyretins, serum samples were analyzed by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry with the Q10 ProteinChip (Bio-Rad, Hercules, CA, USA), a strong anion exchange array with quaternary amine functionality, as described previously. 19 …”

Section: Nephelometry To Measure Serum Transthyretin Concentrations Amentioning

confidence: 99%

Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis

et al. 2015

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Amyloidosis is a protein conformational disorder with the distinctive feature of extracellular accumulation of amyloid fibrils that come from different proteins. In the ligamentum flavum of the lumbar spine, amyloid deposits were frequently found in elderly patients with lumbar spinal canal stenosis and were at least partially formed by wild-type transthyretin. However, how amyloid deposits in the ligamentum flavum affect lumbar spinal canal stenosis has remained unclear. In this study, we analyzed clinical, pathologic, and radiologic findings of patients with lumbar spinal canal stenosis who had amyloid deposits in the ligamentum flavum. We studied 95 ligamentum flavum specimens obtained from 56 patients with lumbar spinal canal stenosis and 21 ligamentum flavum specimens obtained from 19 patients with lumbar disk herniation. We evaluated histopathologic findings and clinicoradiologic manifestations, such as thickness of the ligamentum flavum and lumbar spinal segmental instability. We found that all 95 ligamentum flavum specimens resected from patients with lumbar spinal canal stenosis had amyloid deposits, which we classified into two types, transthyretin-positive and transthyretinnegative, and that transthyretin amyloid formation in the ligamentum flavum of patients with lumbar spinal canal stenosis was an age-associated phenomenon. The amount of amyloid in the ligamentum flavum was related to clinical manifestations of lumbar spinal canal stenosis, such as thickness of the ligamentum flavum and lumbar spinal segmental instability, in the patients with lumbar spinal canal stenosis with transthyretin-positive amyloid deposits. To our knowledge, this report is the first to show clinicopathologic correlations in transthyretin amyloid deposits of the ligamentum flavum. In conclusion, transthyretin amyloid deposits in the ligamentum flavum may be related to the pathogenesis of lumbar spinal canal stenosis in elderly patients.

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Section: Nephelometry To Measure Serum Transthyretin Concentrations Amentioning

confidence: 99%

Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis

et al. 2015

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“…The lower limit of separation minimum mass difference between two molecules could be separated in this system is thought to be about 15 Da, based on the present and previous studies. 5 We were able to separate Leu55Pro and Ala25Ser mutants, which theoretically have a mass shift of 16 Da from WT TTR but were not able to separate Lys35Asn and Ile107Val mutants, which theoretically have a mass shift of 14 Da from WT TTR. 5 SELDI-TOF MS could not separate the atypical TTR variants, whereas succeeded in detecting most variant TTRs, including the common Val30Met TTR.…”

Section: Resultsmentioning

confidence: 73%

“…4 We previously reported a convenient SELDI-TOF MS method that does not require an immunoprecipitation step to detect several types of variant TTR. 5 In this study, we evaluated the clinical usefulness of SELDI-TOF MS for diagnosis of TTR-related amyloidosis.…”

Section: Introductionmentioning

confidence: 99%

Rapid detection of wild-type and mutated transthyretins

et al. 2015

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Background: Familial amyloid polyneuropathy is caused by a variant transthyretin, which is a serum protein secreted by the liver. We previously reported that mutated transthyretins were detected in serum samples by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The aim of this study was to evaluate the clinical usefulness of SELDI-TOF MS for diagnosis of transthyretin-related amyloidosis. Methods: We used 106 serum samples obtained from patients who were clinically suspected of having amyloidosis between February 2011 and April 2014. SELDI-TOF MS allowed analysis for transthyretin via a 3-h one-step procedure. Results: Of the 106 patients, 51 are transthyretin amyloidosis. Mutated transthyretins were detected in serum samples from 30 of 51 patients with transthyretin amyloidosis. The results of genetic analysis showed that all of those patients had mutations in the transthyretin gene. For all 18 patients with senile systemic amyloidosis of 51 patients with transthyretin amyloidosis, SELDI-TOF MS detected only wild-type transthyretin peaks, not mutated transthyretin peaks. Conclusion: SELDI-TOF MS is a clinically useful tool for diagnosis of transthyretin-related amyloidosis.

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“…Approximately 80% of total TTR is conjugated and posttranslationally modified in serum as shown by electrospray ionization (ESI)-mass spectrometry (MS)/MS (Ueda et al, 2009). In this study, we used isoelectric focusing and TTR western blotting and found that nitric oxide-mediated modification of serum TTR occurs when reacted with the MPO/H 2 O 2 system (Figure 4).…”

Section: Discussionmentioning

confidence: 88%

Effect of MPO/H2O2/NO- system on nitric oxide-mediated modification of TTR amyloid and serum TTR in FAP ATTR Val30Met patients

et al. 2014

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ABSTRACT. Amyloid deposits consist of protein fibrils and amorphous material, and this deposition is related to oxidative stress. Previously, we demonstrated the presence of high-density lipoproteins and/or lipids in amyloid deposits of familial amyloid polyneuropathy patients. In this study, the presence of myeloperoxidase (MPO) in amyloid deposits was demonstrated using immunohistochemical staining. In contrast, normal surrounding tissues were consistently negative for MPO. Nitrotyrosine was present in amyloid deposits after being exposed to the MPO/H 2 O 2 / NO -system by immunohistochemical staining, and the oxide mediated modification of serum transthyretin (TTR) was observed upon exposure to the MPO/H 2 O 2 system using two-dimensional gel electrophoresis and TTR Western blotting. This observation revealed that the TTR amyloid deposits and serum TTR were oxidized by the MPO/H 2 O 2 /NO -system. Nitric oxide-mediated modification of TTR may play a role in

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SELDI-TOF Mass Spectrometry Evaluation of Variant Transthyretins for Diagnosis and Pathogenesis of Familial Amyloidotic Polyneuropathy

Cited by 56 publications

References 18 publications

Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis

Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis

Rapid detection of wild-type and mutated transthyretins

Effect of MPO/H2O2/NO- system on nitric oxide-mediated modification of TTR amyloid and serum TTR in FAP ATTR Val30Met patients

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