{"title":"Anti-PEG antibodies associated with reduced therapeutic effect of patisiran in patients with hereditary transthyretin amyloidosis.","authors":"Björn Pilebro, Jonas Wixner, Intissar Anan","doi":"10.1080/13506129.2024.2388713","DOIUrl":"https://doi.org/10.1080/13506129.2024.2388713","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Johan Bijzet, Hans L A Nienhuis, Bart-Jan Kroesen, Arjan Diepstra, Bouke P C Hazenberg
{"title":"ELISA-4-amyloid: diagnostic accuracy of an ELISA panel for typing the four main types of systemic amyloidosis in subcutaneous abdominal fat tissue samples.","authors":"Johan Bijzet, Hans L A Nienhuis, Bart-Jan Kroesen, Arjan Diepstra, Bouke P C Hazenberg","doi":"10.1080/13506129.2024.2385977","DOIUrl":"10.1080/13506129.2024.2385977","url":null,"abstract":"<p><strong>Background: </strong>Reliable typing of amyloid is essential. Amyloid extraction from tissue enables immunochemical typing of the precursor protein using an enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Objective: </strong>To assess the diagnostic accuracy of a panel of ELISAs for typing the four main types (AA, ATTR, AL-kappa and AL-lambda amyloid).</p><p><strong>Methods: </strong>From 1996 to 2023 subcutaneous abdominal fat tissue aspirates were obtained from 1339 amyloidosis patients and 868 controls. Amyloid was visually graded 0-4+ in Congo red-stained smears. Amyloid extracted from tissue by Guanidine was typed using a panel comprising four ELISAs.</p><p><strong>Results: </strong>All amyloid protein concentrations in extracts correlated with amyloid grade in smears. Typing sensitivity was low (23.3%) in samples with grade 1+/2+ amyloid. Overall typing sensitivity of the panel was 81.6% for all easily visible amyloid (grade 3+/4+): high for AA (98.8%) and ATTR (96.8%) and fair for AL-kappa (66.7%) and AL-lambda (75.9). Overall typing specificity was 98.0% and the overall positive predictive value was 98.0%.</p><p><strong>Conclusions: </strong>We describe a highly specific ELISA panel for routine typing of the main amyloid types in fat tissue. Until more sensitive typing techniques will become generally available, typing easily visible amyloid in fat tissue using this ELISA panel is reliable, affordable and straightforward.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical and molecular insights into A97S variants in hereditary transthyretin amyloid polyneuropathy in South China.","authors":"Qingping Wang, Mengdie Wang, Xiying Zhu, Lei Liu, Mengli Wang, Jialu Sun, Xiaobo Li, Shunxiang Huang, Wanqian Cao, Yu Liu, Ruxu Zhang","doi":"10.1080/13506129.2024.2383467","DOIUrl":"https://doi.org/10.1080/13506129.2024.2383467","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to delineate the clinical profiles of the hereditary transthyretin amyloid polyneuropathy (ATTRv-PN) patients with A97S variant from southern China and the molecular characteristics of this mutant protein.</p><p><strong>Methods: </strong>Fifteen ATTRv-PN patients with heterozygous A97S and one patient with homozygous A97S were included in the study. Serum TTR tetramer concentration was quantified through ultra-performance liquid chromatography. Stabilities of A97S-TTR were assessed through <i>in vitro</i> urea-mediated tryptophan fluorescence experiments, and nephelometry was employed in drug response assessment.</p><p><strong>Results: </strong>All patients were late-onset (≥50 years) with a mean age of onset at 59.26 ± 5.06 years old. Patients displayed a mixed phenotype featuring sensory-motor neuropathy with autonomic dysfunction and cardiac involvement, such as palpitations and chest pain. Electrophysiological studies showed generally axonal impairment of sensory and motor nerves. Tafamidis-treated patients showed significantly higher TTR tetramer concentrations, approaching healthy controls' levels. <i>In vitro</i> assessment showed that A97S-TTR was more kinetically stable than the V122I-TTR, and tetramer stabilisers inhibited A97S-TTR amyloid formation by more than 70%.</p><p><strong>Conclusion: </strong>This study provides valuable insights into the clinical and molecular characteristics of ATTRv-PN patients with A97S from South China, particularly regarding the differences in disease progression and stability features.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Altered connectivity of central autonomic network: effects of dysautonomia in hereditary transthyretin amyloidosis with polyneuropathy.","authors":"Tsai-Jou Su, Chien-Ho Janice Lin, Yen-Lin Liu, Hsueh-Wen Hsueh, Sung-Tsang Hsieh, Chi-Chao Chao, Ming-Chang Chiang","doi":"10.1080/13506129.2024.2383450","DOIUrl":"https://doi.org/10.1080/13506129.2024.2383450","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive fatal disorder caused by deposition of mutant transthyretin (TTR) amyloids mainly in the nerves and heart. Autonomic dysfunction is a major disabling manifestation, affecting 90% of patients with late-onset ATTRv-PN. The current study aimed to investigate brain functional alterations associated with dysautonomia due to peripheral autonomic nerve degeneration in ATTRv-PN.</p><p><strong>Methods: </strong>Resting-state functional MRI data were acquired from 43 ATTRv-PN patients predominantly of A97S (p.A117S) genotype, and the functional connectivity of central autonomic regions was assessed.</p><p><strong>Results: </strong>Compared with age-matched healthy controls, the ATTRv-PN patients exhibited (1) reduced functional connectivity of the central autonomic regions such as hypothalamus, amygdala, anterior insula, and middle cingulate cortex with brain areas of the limbic, frontal, and somatosensory systems, and (2) correlations of reduced functional autonomic connectivity with the severity of autonomic dysfunction especially orthostatic intolerance, decreased heart rate variability, and greater clinical disability.</p><p><strong>Conclusions: </strong>Our findings provide evidence linking peripheral autonomic dysfunction with altered connectivity in the central autonomic network in ATTRv-PN.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Noel Estrada-Merly, Mathew S Maurer, Anita D'Souza
{"title":"Glaucoma is not seen at a higher prevalence in age-related transthyretin amyloidosis after race stratification.","authors":"Noel Estrada-Merly, Mathew S Maurer, Anita D'Souza","doi":"10.1080/13506129.2024.2379394","DOIUrl":"https://doi.org/10.1080/13506129.2024.2379394","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Changes in the amyloid editorial board members and in editor positions.","authors":"Stefan Schönland, Per Westermark","doi":"10.1080/13506129.2024.2344167","DOIUrl":"https://doi.org/10.1080/13506129.2024.2344167","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mass spectrometry-based proteomic analysis of proteins adsorbed by hexadecyl-immobilized cellulose bead column for the treatment of dialysis-related amyloidosis.","authors":"Suguru Yamamoto, Keiko Yamamoto, Yoshitoshi Hirao, Keiichi Yamaguchi, Kichitaro Nakajima, Mami Sato, Miho Kawachi, Mio Domon, Kei Goto, Kentaro Omori, Noriaki Iino, Hisaki Shimada, Ryuzi Aoyagi, Isei Ei, Shin Goto, Yuji Goto, Fumitake Gejyo, Tadashi Yamamoto, Ichiei Narita","doi":"10.1080/13506129.2024.2315148","DOIUrl":"10.1080/13506129.2024.2315148","url":null,"abstract":"<p><strong>Background: </strong>Dialysis-related amyloidosis (DRA) is a severe complication in end-stage kidney disease (ESKD) patients undergoing long-term dialysis treatment, characterized by the deposition of β<sub>2</sub>-microglobulin-related amyloids (Aβ2M amyloid). To inhibit DRA progression, hexadecyl-immobilized cellulose bead (HICB) columns are employed to adsorb circulating β<sub>2</sub>-microglobulin (β2M). However, it is possible that the HICB also adsorbs other molecules involved in amyloidogenesis.</p><p><strong>Methods: </strong>We enrolled 14 ESKD patients using HICB columns for DRA treatment; proteins were extracted from HICBs following treatment and identified using liquid chromatography-linked mass spectrometry. We measured the removal rate of these proteins and examined the effect of those molecules on Aβ2M amyloid fibril formation <i>in vitro</i>.</p><p><strong>Results: </strong>We identified 200 proteins adsorbed by HICBs. Of these, 21 were also detected in the amyloid deposits in the carpal tunnels of patients with DRA. After passing through the HICB column and hemodialyzer, the serum levels of proteins such as β2M, lysozyme, angiogenin, complement factor D and matrix Gla protein were reduced. These proteins acted in the Aβ2M amyloid fibril formation.</p><p><strong>Conclusions: </strong>HICBs adsorbed diverse proteins in ESKD patients with DRA, including those detected in amyloid lesions. Direct hemoperfusion utilizing HICBs may play a role in acting Aβ2M amyloidogenesis by reducing the amyloid-related proteins.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Antonia S Carroll, Yousuf Razvi, Luke O'Donnell, Elena Veleva, Amanda Heslegrave, Henrik Zetterberg, Steve Vucic, Matthew C Kiernan, Alexander M Rossor, Julian D Gillmore, Mary M Reilly
{"title":"Serum neurofilament light chain in hereditary transthyretin amyloidosis: validation in real-life practice.","authors":"Antonia S Carroll, Yousuf Razvi, Luke O'Donnell, Elena Veleva, Amanda Heslegrave, Henrik Zetterberg, Steve Vucic, Matthew C Kiernan, Alexander M Rossor, Julian D Gillmore, Mary M Reilly","doi":"10.1080/13506129.2024.2313218","DOIUrl":"10.1080/13506129.2024.2313218","url":null,"abstract":"<p><strong>Background: </strong>Neurofilament light chain (NfL) has emerged as a sensitive biomarker in hereditary transthyretin amyloid polyneuropathy (ATTRv-PN). We hypothesise that NfL can identify conversion of gene carriers to symptomatic disease, and guide treatment approaches.</p><p><strong>Methods: </strong>Serum NfL concentration was measured longitudinally (2015-2022) in 59 presymptomatic and symptomatic ATTR variant carriers. Correlations between NfL and demographics, biochemistry and staging scores were performed as well as longitudinal changes pre- and post-treatment, and in asymptomatic and symptomatic cohorts. Receiver-operating analyses were performed to determine cut-off values.</p><p><strong>Results: </strong>NfL levels correlated with examination scores (CMTNS, NIS and MRC; all <i>p</i> < .01) and increased with disease severity (PND and FAP; all <i>p</i> < .05). NfL was higher in symptomatic and sensorimotor converters, than asymptomatic or sensory converters irrespective of time (all <i>p</i> < .001). Symptomatic or sensorimotor converters were discriminated from asymptomatic patients by NfL concentrations >64.5 pg/ml (sensitivity= 91.9%, specificity = 88.5%), whereas asymptomatic patients could only be discriminated from sensory or sensorimotor converters or symptomatic individuals by a NfL concentration >88.9 pg/ml (sensitivity = 62.9%, specificity = 96.2%) However, an NfL increment of 17% over 6 months could discriminate asymptomatic from sensory or sensorimotor converters (sensitivity = 88.9%, specificity = 80.0%). NfL reduced with treatment by 36%/year and correlated with TTR suppression (<i>r</i> = 0.64, <i>p</i> = .008).</p><p><strong>Conclusions: </strong>This data validates the use of serum NfL to identify conversion to symptomatic disease in ATTRv-PN. NfL levels can guide assessment of disease progression and response to therapies.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicholas S Hendren, James A De Lemos, Jarett D Berry, Julia Kozlitina, Lorena Saelices, Alan X Ji, Zhili Shao, Chia-Feng Liu, Sonia Garg, Maryjane A Farr, Mark H Drazner, W H Wilson Tang, Justin L Grodin
{"title":"Circulating transthyretin and retinol binding protein 4 levels among middle-age V122I <i>TTR</i> carriers in the general population.","authors":"Nicholas S Hendren, James A De Lemos, Jarett D Berry, Julia Kozlitina, Lorena Saelices, Alan X Ji, Zhili Shao, Chia-Feng Liu, Sonia Garg, Maryjane A Farr, Mark H Drazner, W H Wilson Tang, Justin L Grodin","doi":"10.1080/13506129.2024.2322479","DOIUrl":"10.1080/13506129.2024.2322479","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has a long latency phase before clinical onset, creating a need to identify subclinical disease. We hypothesized circulating transthyretin (TTR) and retinol binding protein 4 (RBP4) levels would be associated with <i>TTR</i> carrier status and correlated with possible evidence of subclinical ATTRv-CA.</p><p><strong>Methods: </strong>TTR and RBP4 were measured in blood samples from V122I <i>TTR</i> carriers and age-, sex- and race-matched non-carrier controls (1:2 matching) among Dallas Heart Study participants (phases 1 (DHS-1) and 2 (DHS-2)). Multivariable linear regression models determined factors associated with TTR and RBP4.</p><p><strong>Results: </strong>There were 40 V122I <i>TTR</i> carriers in DHS-1 and 54 V122I <i>TTR</i> carriers in DHS-2. In DHS-1 and DHS-2, TTR was lower in V122I <i>TTR</i> carriers (<i>p</i> < .001 for both), and RBP4 in DHS-2 was lower in V122I <i>TTR</i> carriers than non-carriers (<i>p</i> = .002). Among V122I <i>TTR</i> carriers, TTR was negatively correlated with markers of kidney function, and limb lead voltage (<i>p</i> < .05 for both) and TTR and RBP4 were correlated with atrial volume in DHS-2 (<i>p</i> < .05).</p><p><strong>Conclusions: </strong>V122I TTR carrier status is independently associated with lower TTR and RBP4 in comparison with non-carriers. These findings support the hypothesis that TTR and RBP4 may correlate with evidence of subclinical ATTRv-CA.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140040849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Milou Berends, Anne F Brunger, Johan Bijzet, Bart-Jan Kroesen, Gea Drost, Fiete Lange, Charlotte E Teunissen, Sjors In 't Veld, Alexander Fje Vrancken, Reinold O B Gans, Bouke P C Hazenberg, Paul A van der Zwaag, Hans L A Nienhuis
{"title":"Longitudinal analysis of serum neurofilament light chain levels as marker for neuronal damage in hereditary transthyretin amyloidosis.","authors":"Milou Berends, Anne F Brunger, Johan Bijzet, Bart-Jan Kroesen, Gea Drost, Fiete Lange, Charlotte E Teunissen, Sjors In 't Veld, Alexander Fje Vrancken, Reinold O B Gans, Bouke P C Hazenberg, Paul A van der Zwaag, Hans L A Nienhuis","doi":"10.1080/13506129.2024.2327342","DOIUrl":"10.1080/13506129.2024.2327342","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate serum neurofilament light chain (sNfL) as biomarker of disease onset, progression and treatment effect in hereditary transthyretin (ATTRv) amyloidosis patients and <i>TTR</i> variant (<i>TTR</i>v) carriers.</p><p><strong>Methods: </strong>sNfL levels were assessed longitudinally in persistently asymptomatic <i>TTR</i>v carriers (<i>N</i> = 12), persistently asymptomatic ATTRv amyloidosis patients (defined as asymptomatic patients but with amyloid detectable in subcutaneous abdominal fat tissue) (<i>N</i> = 8), in <i>TTR</i>v carriers who developed polyneuropathy (<i>N</i> = 7) and in ATTRv amyloidosis patients with polyneuropathy on treatment (TTR-stabiliser (<i>N</i> = 20) or TTR-silencer (<i>N</i> = 18)). Polyneuropathy was confirmed by nerve conduction studies or quantitative sensory testing. sNfL was analysed using a single-molecule array assay.</p><p><strong>Results: </strong>sNfL increased over 2 years in persistently asymptomatic ATTRv amyloidosis patients, but did not change in persistently asymptomatic <i>TTR</i>v carriers. In all <i>TTR</i>v carriers who developed polyneuropathy, sNfL increased from 8.4 to 49.8 pg/mL before the onset of symptoms and before polyneuropathy could be confirmed neurophysiologically. In symptomatic ATTRv amyloidosis patients on a TTR-stabiliser, sNfL remained stable over 2 years. In patients on a TTR-silencer, sNfL decreased after 1 year of treatment.</p><p><strong>Conclusion: </strong>sNfL is a biomarker of early neuronal damage in ATTRv amyloidosis already before the onset of polyneuropathy. Current data support the use of sNfL in screening asymptomatic <i>TTR</i>v carriers and in monitoring of disease progression and treatment effect.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}