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Clinical Chemistry 55: 1223-1227, 2009. First published April 16, 2009; 10.1373/clinchem.2008.118505
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(Clinical Chemistry. 2009;55:1223-1227.)
© 2009 American Association for Clinical Chemistry, Inc.

Brief Communications

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

Mitsuharu Ueda1,a, Yohei Misumi2, Mineyuki Mizuguchi3, Masaaki Nakamura4, Taro Yamashita2, Yoshiki Sekijima5, Kazutoshi Ota1, Satoru Shinriki1, Hirofumi Jono1, Shu-ichi Ikeda5, Ole B. Suhr6 and Yukio Ando1

1 Department of Diagnostic Medicine and2 Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;3 Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan;4 Clinical Medicine Section, Department of Clinical Medicine, National Institute for Minamata Disease, Kumamoto, Japan;5 Department of Neurology and Rheumatology, Shinshu University School of Medicine, Matsumoto, Japan;6 Department of Medicine, Umeå University Hospital, Umeå, Sweden;

aaddress correspondence to this author at: Department of Diagnostic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-0811, Japan. Fax +81-96-362-7540, e-mail mueda5{at}fc.kuh.kumamoto-u.ac.jp.


Abstract

Background: Mass spectrometric analyses are valuable for detection of transthyretin (TTR) variants, which cause familial amyloidotic polyneuropathy (FAP). However, those methods require an immunoprecipitation step with an anti-TTR antibody and are not suitable for quantitative detection. We investigated the usefulness of SELDI-TOF mass spectrometry (MS) without an immunoprecipitation step.

Methods: We used ProteinChips with chromatographic capture formats to detect TTRs. We attempted to correlate the intensity of mixed samples of amyloidogenic TTR (ATTR) V30M to wild-type (WT) TTR. We analyzed the proportion of ATTR V30M in amyloid-laden cardiac tissues from FAP patients, and also evaluated samples from FAP patients with 16 other TTR mutations.

Results: Detection of ATTR required only 3 h of SELDI-TOF MS analysis. We determined that SELDI-TOF MS was suitable for quantitative detection of ATTR V30M and demonstrated that the proportion of ATTR V30M to WT TTR was 46.6% in amyloid-laden cardiac tissue from an FAP patient who died 10 years after liver transplantation. With this method, we identified 12 of 17 TTR variants. Small mass shifts and low concentrations of variants prevented ATTR detection. By changing the analytical conditions, we achieved detection of low concentrations of ATTR Y114C in serum.

Conclusions: SELDI-TOF MS is a reliable tool for quantitative evaluation of TTR variants, in both tissue amyloid deposits and body fluids. This method is useful for the diagnosis and investigation of the pathogenesis of FAP.






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