Unusual Self-Association Properties of Transthyretin Y114C Related to Familial Amyloidotic Polyneuropathy: Effects on Detection and Quantification

We performed biochemical and immunological examinations of heterozygotic carriers of the transthyretin (TTR) mutant Y114C associated with familial amyloidotic polyneuropathy (FAP). The total serum TTR levels in Y114C TTR carriers were extremely low when analyzed by single radial immunodiffusion (SRI...

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Published in:Biochemical and biophysical research communications 1999-08, Vol.261 (2), p.264-269
Main Authors: Ando, Yukio, Almeida, Maria do Rosário, Ohlsson, Per-Ingvar, Ando, Eiko, Negi, Akira, Suhr, Ole, Terazaki, Hisayasu, Obayashi, Konen, Ando, Masayuki, Saraiva, Maria J.M.
Format: Article
Language:English
Subjects:
Adult
Amyloid Neuropathies - blood
Amyloid Neuropathies - genetics
Enzyme-Linked Immunosorbent Assay
familial amyloidotic polyneuropathy
FAP
Female
Heterozygote
Humans
Immunochemistry
Mass Spectrometry
Middle Aged
Molecular Weight
Point Mutation
Prealbumin - chemistry
Prealbumin - genetics
Prealbumin - metabolism
Recombinant Proteins - genetics
Recombinant Proteins - immunology
transthyretin
transthyretin, amyloid
Y114C TTR
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Summary:We performed biochemical and immunological examinations of heterozygotic carriers of the transthyretin (TTR) mutant Y114C associated with familial amyloidotic polyneuropathy (FAP). The total serum TTR levels in Y114C TTR carriers were extremely low when analyzed by single radial immunodiffusion (SRID), whereas by indirect enzyme-linked immunosorbent assay (ELISA) procedure, their total TTR concentrations were increased. Recombinant homozygotic Y114C TTR showed no immunoreactivity towards a TTR antibody when analyzed by SRID, whereas by the ELISA procedure presented the same degree of reactivity as that of normal TTR or isolated serum heterozygotic Y114C TTR. These results indicate that immunodifusion based techniques cannot properly determine TTR serum levels in Y114C carriers. Analyses of serum TTR of the Y114C TTR carriers by electrospray ionization mass spectrometry (ESI-MS) with the orifice corn voltage at 60 V revealed a small peak of the free Y114C TTR in addition to large TTR peaks of normal TTR. The levels of the free mutant TTR increased with the orifice corn voltage at 90 V. In contrast, increase in orifice voltage from 60 to 90 V produced a reduction in the level of normal TTR. The results suggest a different pattern of association between monomers in Y114C relative to normal TTR.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.1048