Amyloid-Journal of Protein Folding Disorders最新文献_第4页

Response to therapy with tafamidis 61 mg in patients with cardiac transthyretin amyloidosis: real-world experience since approval. 心脏转甲状腺素淀粉样变性患者对他法米迪 61 毫克治疗的反应：获批后的实际体验。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-09-01 Epub Date: 2024-07-17 DOI: 10.1080/13506129.2024.2376202

Fabian Aus dem Siepen, Christopher Meissner, Eva Hofmann, Selina Hein, Christian Nagel, Ute Hegenbart, Stefan O Schönland, Florian Andre, Norbert Frey, Arnt V Kristen

{"title":"Response to therapy with tafamidis 61 mg in patients with cardiac transthyretin amyloidosis: real-world experience since approval.","authors":"Fabian Aus dem Siepen, Christopher Meissner, Eva Hofmann, Selina Hein, Christian Nagel, Ute Hegenbart, Stefan O Schönland, Florian Andre, Norbert Frey, Arnt V Kristen","doi":"10.1080/13506129.2024.2376202","DOIUrl":"10.1080/13506129.2024.2376202","url":null,"abstract":"Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease that causes heart failure due to amyloid fibril deposition. Tafamidis was approved as the first causal treatment in 2020. We here report on real-world data in patients treated with tafamidis for at least 12 months according to the recently defined European Society for Cardiology (ESC) consensus criteria for disease progression.Methods and results: Three hundred and eight wildtype and 31 hereditary ATTR-CM patients were prospectively enrolled after first diagnosis of ATTR-CM and initiation of tafamidis 61 mg once daily treatment. After 12 months, significant deterioration in Karnofsky Index, estimated glomerular filtration rate (eGFR), N-terminal brain natriuretic peptide (NT-proBNP), septum thickness and left ventricular ejection fraction (LVEF) could be observed, significant disease progression was only detected in 25 patients (9%) using ESC consensus criteria. Mean survival time was 37 months with no differences between responders and non-responders. NT-proBNP was the only independent predictor for poor therapy response (p = .008).Conclusions: The majority of patients showed no significant disease progression according to the ESC consensus criteria after 12 months of therapy with tafamidis. However, at 12 months, treatment response based on the ESC consensus criteria was not associated with improved survival. Moreover, higher levels of NT-proBNP at diagnosis of ATTR-CM appears to predict poorer treatment response, confirming that timely initiation of therapy is advantageous.","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"226-231"},"PeriodicalIF":5.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141635594","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}

引用次数: 0

Double pathogenic variant in an ATTRv patient with mixed phenotype. 一名混合表型 ATTRv 患者的双重致病变体。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-09-01 Epub Date: 2024-05-16 DOI: 10.1080/13506129.2024.2346536

Maria Ausilia Sciarrone, Rosa Lillo, Angela Romano, Francesca Vitali, Valeria Guglielmino, Maria Chiara Meucci, Francesca Graziani, Marco Luigetti

引用次数: 0

Genetic counselling for at-risk family members with hereditary transthyretin amyloidosis: data from a single-centre study. 为遗传性转甲状腺素淀粉样变性的高危家庭成员提供遗传咨询：一项单中心研究的数据。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-09-01 Epub Date: 2024-05-25 DOI: 10.1080/13506129.2024.2357094

Katsuya Nakamura, Tsuneaki Yoshinaga, Akiko Sakyu, Akira Matsushima, Yuka Yonehara, Tomomi Kojima, Masumi Ishikawa, Emiko Kise, Tomoki Kosho, Yoshiki Sekijima

{"title":"Genetic counselling for at-risk family members with hereditary transthyretin amyloidosis: data from a single-centre study.","authors":"Katsuya Nakamura, Tsuneaki Yoshinaga, Akiko Sakyu, Akira Matsushima, Yuka Yonehara, Tomomi Kojima, Masumi Ishikawa, Emiko Kise, Tomoki Kosho, Yoshiki Sekijima","doi":"10.1080/13506129.2024.2357094","DOIUrl":"10.1080/13506129.2024.2357094","url":null,"abstract":"Background: Hereditary transthyretin-related amyloidosis is an autosomal dominant disorder. Recently, disease-modifying therapies (DMTs) have been developed. For at-risk individuals, genetic analysis aids in the early administration of medical care; however, few studies have evaluated the current status of genetic counselling and management of presymptomatic carriers of amyloidogenic variants.Methods: We retrospectively evaluated the medical records of 202 consecutive participants.Results: A total of 103 clients who received genetic counselling for predictive testing were at-risk, and 83 underwent predictive testing. Genetic testing results were positive in 33 patients, 11 of whom had confirmed amyloid deposition and were administered DMTs. For presymptomatic V30M (p.V50M) carriers, 32.0 ± 2.4 years (median ± standard error) was the age when amyloid deposition was first identified (95% confidence interval 27.4-36.6). Serum transthyretin (TTR) levels decreased serially with an estimated slope of -1.2 mg/dL/year.Conclusions: Our study suggests the clinical utility of management using a combination of predictive testing and monitoring methods. Psychosocial support should be considered with collaboration between geneticists/genetic counsellors and psychologists. For a more optimised protocol for monitoring and designing future interventional trials in presymptomatic carriers, prospective cohort studies are necessary to clarify the natural history, particularly in the early stages of the disease.","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"179-183"},"PeriodicalIF":5.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141096812","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}

引用次数: 0

Outcomes of venetoclax-based therapy in patients with t(11;14) light chain amyloidosis after failure of daratumumab-based therapy. 达拉单抗治疗失败后，t(11;14)轻链淀粉样变性患者接受venetoclax治疗的疗效。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-09-01 Epub Date: 2024-07-02 DOI: 10.1080/13506129.2024.2366806

Danai Dima, Michael Hughes, Mark Orland, Fauzia Ullah, Utkarsh Goel, Faiz Anwer, Shahzad Raza, Sandra Mazzoni, Divaya Bhutani, Louis Williams, Suzanne Lentzsch, Christy Samaras, Jason Valent, Rajshekhar Chakraborty, Jack Khouri

{"title":"Outcomes of venetoclax-based therapy in patients with t(11;14) light chain amyloidosis after failure of daratumumab-based therapy.","authors":"Danai Dima, Michael Hughes, Mark Orland, Fauzia Ullah, Utkarsh Goel, Faiz Anwer, Shahzad Raza, Sandra Mazzoni, Divaya Bhutani, Louis Williams, Suzanne Lentzsch, Christy Samaras, Jason Valent, Rajshekhar Chakraborty, Jack Khouri","doi":"10.1080/13506129.2024.2366806","DOIUrl":"10.1080/13506129.2024.2366806","url":null,"abstract":"Background: Daratumumab's incorporation in the upfront treatment of light chain (AL) amyloidosis has led to daratumumab (dara) refractoriness early in disease course. Patients who experience relapse or have suboptimal response to dara-based-therapy, have limited options.Objective: This study aimed to evaluate the outcomes of venetoclax-based therapy in t(11;14) positive AL patients who previously failed dara.Methods: Thirty-one patients with AL were included in this bi-institutional retrospective analysis.Results: Dara failure was due to inadequate response in 20 (65%) patients, haematologic relapse in 7 (22%), and both haematologic plus organ relapse in 4 (13%). Overall haematologic response rate to venetoclax-based therapy was 97%, with ≥ VGPR being 91%. Of the 19 evaluable patients with cardiac involvement, 14 (74%) achieved organ response. Of the 13 evaluable patients with renal involvement, 6 (46%) achieved organ response. With a median follow-up of 22 months, median time-to-next-treatment (TTNT) and overall survival (OS) were not reached. The 12- and 24-month TTNT rates were 74% and 56%, respectively. At data-cut-off, four patients had died, all from AL-related organ complications. The 12- and 24-month OS rates were 89% and 85%, respectively. Grade ≥3 adverse events occurred in 26% of patients, with 6% due to infections.Conclusion: These findings are encouraging for the use of venetoclax as salvage therapy post-dara failure.","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"195-201"},"PeriodicalIF":5.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494182","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}

引用次数: 0

Internalisation of immunoglobulin light chains by cardiomyocytes in AL amyloidosis: what can biopsies tell us? AL 淀粉样变性病中心肌细胞对免疫球蛋白轻链的内化：活检能告诉我们什么？

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-09-01 Epub Date: 2024-07-07 DOI: 10.1080/13506129.2024.2373748

Mélanie Bézard, Amira Zaroui, Mounira Kharoubi, France Lam, Elsa Poullot, Emmanuel Teiger, Onnik Agbulut, Thibaud Damy, Ekaterini Kordeli

{"title":"Internalisation of immunoglobulin light chains by cardiomyocytes in AL amyloidosis: what can biopsies tell us?","authors":"Mélanie Bézard, Amira Zaroui, Mounira Kharoubi, France Lam, Elsa Poullot, Emmanuel Teiger, Onnik Agbulut, Thibaud Damy, Ekaterini Kordeli","doi":"10.1080/13506129.2024.2373748","DOIUrl":"10.1080/13506129.2024.2373748","url":null,"abstract":"Background: Cardiac involvement in systemic light chain amyloidosis (AL) leads to chronic heart failure and is a major prognosis factor. Severe cellular defects are provoked in cardiac cells by tissue-deposited amyloid fibrils of misfolded free immunoglobulin light chains (LCs) and their prefibrillar oligomeric precursors.Objective: Understanding the molecular mechanisms behind cardiac cell cytotoxicity is necessary to progress in therapy and to improve patient management. One key question is how extracellularly deposited molecules exert their toxic action inside cardiac cells. Here we searched for direct evidence of amyloid LC uptake by cardiomyocytes in patient biopsies.Methods: We immunolocalized LCs in cardiac biopsies from four AL cardiac amyloidosis patients and analysed histopathological images by high resolution confocal microscopy and 3D image reconstruction.Results: We show, for the first time directly in patient tissue, the presence of LCs inside cardiomyocytes, and report their proximity to nuclei and to caveolin-3-rich areas. Our observations point to macropinocytosis as a probable mechanism of LC uptake.Conclusions: Internalisation of LCs occurs in patient cardiomyocytes. This event could have important consequences for the pathogenesis of the cardiac disease by enabling interactions between amyloid molecules and cellular organelles inducing specific signalling pathways, and might bring new insight regarding treatment.","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"209-219"},"PeriodicalIF":5.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555886","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}

引用次数: 0

Identification of isoaspartate-modified transthyretin as potential target for selective immunotherapy of transthyretin amyloidosis. 鉴定异天门冬氨酸修饰的转甲状腺素，作为转甲状腺素淀粉样变性选择性免疫疗法的潜在靶点。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-09-01 Epub Date: 2024-05-27 DOI: 10.1080/13506129.2024.2358121

Janett Köppen, Martin Kleinschmidt, Markus Morawski, Jens-Ulrich Rahfeld, Michael Wermann, Holger Cynis, Ute Hegenbart, Christoph Daniel, Steffen Roßner, Stephan Schilling, Anja Schulze

{"title":"Identification of isoaspartate-modified transthyretin as potential target for selective immunotherapy of transthyretin amyloidosis.","authors":"Janett Köppen, Martin Kleinschmidt, Markus Morawski, Jens-Ulrich Rahfeld, Michael Wermann, Holger Cynis, Ute Hegenbart, Christoph Daniel, Steffen Roßner, Stephan Schilling, Anja Schulze","doi":"10.1080/13506129.2024.2358121","DOIUrl":"10.1080/13506129.2024.2358121","url":null,"abstract":"Background: Numerous studies suggest a progressive accumulation of post-translationally modified peptides within amyloid fibrils, including isoaspartate (isoD) modifications. Here, we generated and characterised novel monoclonal antibodies targeting isoD-modified transthyretin (TTR). The antibodies were used to investigate the presence of isoD-modified TTR in deposits from transthyretin amyloidosis patients and to mediate antibody-dependent phagocytosis of TTR fibrils.Methods: Monoclonal antibodies were generated by immunisation of mice using an isoD-modified peptide and subsequent hybridoma generation. The antibodies were characterised in terms of affinity and specificity to isoD-modified TTR using surface plasmon resonance, transmission electron microscopy and immunohistochemical staining of human cardiac tissue. The potential to elicit antibody-dependent phagocytosis of TTR fibrils was assessed using THP-1 cells.Results: We developed two mouse monoclonal antibodies, 2F2 and 4D4, with high nanomolar affinity for isoD-modified TTR and strong selectivity over the unmodified epitope. Both antibodies show presence of isoD-modified TTR in human cardiac tissue, but not in freshly purified recombinant TTR, suggesting isoD modification only present in aged fibrillar deposits. Likewise, the antibodies only facilitated phagocytosis of TTR fibrils and not TTR monomers by THP-1 cells.Conclusions: These antibodies label aged, non-native TTR deposits, leaving native TTR unattended and thereby potentially enabling new therapeutic approaches.","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":" ","pages":"184-194"},"PeriodicalIF":5.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155437","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}

引用次数: 0

Absence of an increased wall thickness does not rule out cardiac amyloidosis. 没有心肌壁厚度增加并不能排除心脏淀粉样变性。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-09-01 Epub Date: 2024-05-20 DOI: 10.1080/13506129.2024.2348681

Steven A Muller, Anouk Achten, Manon G van der Meer, Peter-Paul Zwetsloot, Sandra Sanders-van Wijk, Pim van der Harst, J Peter van Tintelen, Anneline S J M Te Riele, Vanessa van Empel, Christian Knackstedt, Marish I F J Oerlemans

引用次数: 0

Possible transmission of leukocyte chemotactic factor 2 amyloidosis after interpopulational liver transplantation. 肝移植后白细胞趋化因子2淀粉样变性的可能传播。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-09-01 Epub Date: 2024-03-05 DOI: 10.1080/13506129.2024.2322480

Yuji Suzuki, Masayoshi Tasaki, Keisuke Kakisaka, Masao Nishiya, Toshiya Nomura, Mitsuki Nakao, Erika Sugawara, Yasuhiro Takikawa, Mitsuharu Ueda

引用次数: 0

Gastrointestinal Amyloid Screening Study (GASS): is screening for amyloid in the gastrointestinal tract useful? 胃肠道淀粉样蛋白筛查研究（GASS）：胃肠道淀粉样蛋白筛查有用吗？

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-09-01 Epub Date: 2024-05-21 DOI: 10.1080/13506129.2024.2347493

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

引用次数: 0

Delayed identification of monoclonal protein is associated with early death in isolated cardiac AL amyloidosis. 单克隆蛋白的延迟鉴定与孤立性心脏 AL 淀粉样变性的早期死亡有关。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-09-01 Epub Date: 2024-07-11 DOI: 10.1080/13506129.2024.2374904

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":"Background: 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.Methods: All patients (n = 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.Results: 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%, p = .008), showing poorer overall survival than those (n = 68, 72%) referred for early M-LC studies (median 3 vs. 14 months, p = .039).Conclusions: Monoclonal protein testing should be the first-step in the diagnostic workup for patients with echocardiographic/other instrumental red flags raising CA suspicion.","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}

引用次数: 0