Rola Khedraki, Joseph El-Roumi, Daniela Allende, Lauren Ives, Ari Garber, Alberto RubioTapia, Jean Paul Achkar, Michael Cline, Brian Baggott, Benjamin Cohen, Florian Rieder, Mazen Hanna
{"title":"Gastrointestinal Amyloid Screening Study (GASS): is screening for amyloid in the gastrointestinal tract useful?","authors":"Rola Khedraki, Joseph El-Roumi, Daniela Allende, Lauren Ives, Ari Garber, Alberto RubioTapia, Jean Paul Achkar, Michael Cline, Brian Baggott, Benjamin Cohen, Florian Rieder, Mazen Hanna","doi":"10.1080/13506129.2024.2347493","DOIUrl":"10.1080/13506129.2024.2347493","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"241-243"},"PeriodicalIF":5.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071702","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}
Paolo Milani, Francesca Fabris, Roberta Mussinelli, Giuseppe Damiano Sanna, Marco Basset, Pietro Benvenuti, Claudia Bellofiore, Martina Nanci, Mario Nuvolone, Andrea Attanasio, Gianluigi Guida, Stefano Perlini, Andrea Foli, Giampaolo Merlini, Giovanni Palladini
{"title":"Delayed identification of monoclonal protein is associated with early death in isolated cardiac AL amyloidosis.","authors":"Paolo Milani, Francesca Fabris, Roberta Mussinelli, Giuseppe Damiano Sanna, Marco Basset, Pietro Benvenuti, Claudia Bellofiore, Martina Nanci, Mario Nuvolone, Andrea Attanasio, Gianluigi Guida, Stefano Perlini, Andrea Foli, Giampaolo Merlini, Giovanni Palladini","doi":"10.1080/13506129.2024.2374904","DOIUrl":"10.1080/13506129.2024.2374904","url":null,"abstract":"<p><strong>Background: </strong>Early identification of immunoglobulin light-chain amyloidosis (AL) is crucial due to its rapid progression. Monoclonal light-chain (M-LC) testing is the first step in the diagnostic workup for patients with suspected cardiac amyloidosis (CA). We aimed to determine whether the time interval between the first CA suspicion and M-LC testing can be related to AL amyloidosis survival outcomes.</p><p><strong>Methods: </strong>All patients (<i>n</i> = 94) with isolated cardiac AL amyloidosis diagnosed at our center between 2016 and 2020 were included. Those with pre-existing known monoclonal protein (monoclonal gammopathy of undetermined significance or smoldering multiple myeloma) were excluded. Time intervals to diagnostic tests and diagnosis were calculated and assessed for their survival prediction ability.</p><p><strong>Results: </strong>The time interval between first CA suspicion (on echocardiography) and M-LC testing correlated with early mortality, and the best cutoff predicting survival, was 6 weeks. The 26 patients (∼28% of entire cohort) who underwent M-LC-studies >6 weeks after first suspicion more frequently presented Mayo stage IIIb (65% vs. 35%, <i>p</i> = .008), showing poorer overall survival than those (<i>n</i> = 68, 72%) referred for early M-LC studies (median 3 vs. 14 months, <i>p</i> = .039).</p><p><strong>Conclusions: </strong>Monoclonal protein testing should be the first-step in the diagnostic workup for patients with echocardiographic/other instrumental red flags raising CA suspicion.</p>","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"220-225"},"PeriodicalIF":5.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581473","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":"31 2","pages":"85"},"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}
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":" ","pages":"124-131"},"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":" ","pages":"132-141"},"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}
{"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":" ","pages":"105-115"},"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":" ","pages":"95-104"},"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}
Ronald Lands, Emily B Martin, Dustin Powell, Alan Stuckey, Bryan Whittle, Spencer Guthrie, Renju Raj, Stephen J Kennel, Jonathan S Wall
{"title":"Longitudinal PET/CT imaging with iodine (<sup>124</sup>I) evuzamitide reveals organ response to plasma cell immunotherapy in a patient with AL amyloidosis.","authors":"Ronald Lands, Emily B Martin, Dustin Powell, Alan Stuckey, Bryan Whittle, Spencer Guthrie, Renju Raj, Stephen J Kennel, Jonathan S Wall","doi":"10.1080/13506129.2023.2286427","DOIUrl":"10.1080/13506129.2023.2286427","url":null,"abstract":"","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"148-149"},"PeriodicalIF":5.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11109018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138292356","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}