| 1. |
- Obayashi, Konen, et al.
(författare)
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Impact of antibodies against amyloidogenic transthyretin (ATTR) on phenotypes of patients with familial amyloidotic polyneuropathy (FAP) ATTR Valine30Methionine
- 2013
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 419C, s. 127-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This study investigated whether a relationship exists between the presence of de novo antibodies and the clinical manifestations of familial amyloidotic polyneuropathy (FAP). METHODS: Serum samples were collected from 25 Japanese and 6 Swedish FAP amyloidogenic transthyretin (ATTR) Valine30Methionine (V30M) patients, 4 asymptomatic Japanese ATTR V30M gene carriers, and 24 Japanese healthy volunteers. Study methods included enzyme-linked immunosorbent assay (ELISA) and mass spectrometry. RESULTS: Three Japanese and 5 Swedish patients had significantly higher levels of antibodies against ATTR than did healthy volunteers and asymptomatic gene carriers (P<0.05). All 8 patients with higher antibody levels were late-onset cases. The ratio of wild-type TTR to ATTR V30M in serum from the high-antibody group was higher than that of the low-antibody group. ELISA results revealed two epitopes at positions 24-35 and 105-115 of ATTR V30M. We found a significant positive correlation between levels of the antibody at positions 24-35 and the age at FAP onset (r=0.751, P<0.05). An age-dependent increase in the occurrence of antibodies was observed in these patients with an epitope at positions 24-35. CONCLUSIONS: These findings may help explain the differences in early- and late-onset FAP and/or the progression of FAP.
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| 2. |
- Oshima, Toshinori, et al.
(författare)
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Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10 years after liver transplantation
- 2014
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 85:7, s. 740-746
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Tidskriftsartikel (refereegranskat)abstract
- Objective To elucidate the long-term effects of liver transplantation (LT) on familial amyloid polyneuropathy (FAP). Methods We investigated clinicopathological and biochemical characteristics of systemic tissues in four autopsied cases of FAP patients surviving more than 10 years after LT and seven autopsied cases without LT. For analysing the truncated form of transthyretin (TTR) in amyloid, we also employed specimens from additional 18 FAP patients. Results Several tissue sites such as the heart, tongue and spinal cord had moderate-to-severe amyloid deposits but other tissues showed no or mild amyloid deposition. Those findings seemed similar to those observed in senile systemic amyloidosis (SSA), a sporadic amyloidosis caused by wild-type (WT) TTR. Also, amyloid deposits in systemic tissue sites except for the spinal cord in patients after LT derived mostly from WT TTR secreted from the normal liver grafts. In addition, in non-transplantation patients, proportions of WT TTR seemed to be relatively high in those tissue sites in which patients after LT had severe amyloid deposition, which suggests that WT TTR tends to form amyloid in those tissue sites. Finally, although the truncation of TTR in amyloid deposits did not depend on undergoing LT, we elucidated the truncation of TTR occurred predominantly in patients from non-endemic areas of Japan, where FAP amyloidogenic TTR V30M patients are late onset and low penetrance, compared with patients from an endemic area of Japan. Conclusions FAP may shift to systemic WT TTR amyloid formation after LT, which seems to be similar to the process in SSA. The truncation of TTR in amyloid deposits may depend on some genetic or environmental factors other than undergoing LT.
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| 3. |
- Ueda, Mitsuharu, et al.
(författare)
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SELDI-TOF mass spectrometry evaluation of variant transthyretins for diagnosis and pathogenesis of familial amyloidotic polyneuropathy.
- 2009
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Ingår i: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 55:6, s. 1223-7
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Tidskriftsartikel (refereegranskat)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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