Amyloid-Journal of Protein Folding Disorders最新文献_第2页

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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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

A report from the European Proteomics Amyloid Network (EPAN). 欧洲蛋白质组学淀粉样蛋白网络（EPAN）的报告。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-08-22 DOI: 10.1080/13506129.2024.2392185

Diana Canetti, Graham W Taylor, Francesca Lavatelli, Christoph Röcken

引用次数: 0

Brain MRI in patients with V30M hereditary transthyretin amyloidosis. V30M 遗传性转甲状腺素淀粉样变性患者的脑磁共振成像。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-08-17 DOI: 10.1080/13506129.2024.2391842

Luísa Sousa, Catarina Pinto, Ana Azevedo, Liliana Igreja, Ana Marta, Joana Fernandes, Pedro Oliveira, Márcio Cardoso, Cristina Alves, Ana Martins da Silva, Miguel Mendonça Pinto, Ana Paula Sousa, Teresa Coelho, Ricardo Taipa

{"title":"Brain MRI in patients with V30M hereditary transthyretin amyloidosis.","authors":"Luísa Sousa, Catarina Pinto, Ana Azevedo, Liliana Igreja, Ana Marta, Joana Fernandes, Pedro Oliveira, Márcio Cardoso, Cristina Alves, Ana Martins da Silva, Miguel Mendonça Pinto, Ana Paula Sousa, Teresa Coelho, Ricardo Taipa","doi":"10.1080/13506129.2024.2391842","DOIUrl":"https://doi.org/10.1080/13506129.2024.2391842","url":null,"abstract":"Background: Central nervous system dysfunction is common in longstanding hereditary transthyretin amyloidosis (ATTRv) caused by the V30M (p.V50M) mutation. Neuropathology studies show leptomeningeal amyloid deposition and cerebral amyloid angiopathy (CAA). Brain MRI is widely used in the assessment of Aβ associated CAA but there are no systematic studies with brain MRI in ATTRv amyloidosis.Methods: we performed 3 T brain MRIs in 16 patients with longstanding (>14 years) ATTRV30M. We additionally retrospectively reviewed 48 brain MRIs from patients followed at our clinic. CNS symptoms and signs were systematically accessed, and MRIs were blindly reviewed for ischaemic and haemorrhagic lesions.Results: in the prospective cohort, we found white matter hyperintensities in 8/16 patients (50%, Fazekas score> =1). There were no relevant microbleeds, large ischaemic or haemorrhagic lesions or superficial siderosis. In the retrospective cohort, microbleeds were found in 5/48 patients (10,4%), two of which with > =20 microbleeds. White matter hyperintensities were found in 20/48 cases (41.7%). White matter lesions, microbleeds and cortical atrophy were not associated with disease duration.Conclusions: white matter hyperintensities are common in ATTRV30M, irrespective of disease duration. Haemorrhagic lesions are rare, even in patients with longstanding disease, suggesting the existence of other risk factors.","PeriodicalId":50964,"journal":{"name":"Amyloid-Journal of Protein Folding Disorders","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996881","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

Anti-PEG antibodies associated with reduced therapeutic effect of patisiran in patients with hereditary transthyretin amyloidosis. 遗传性转甲状腺素淀粉样变性患者的抗PEG抗体与帕替西兰治疗效果降低有关。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-08-10 DOI: 10.1080/13506129.2024.2388713

Björn Pilebro, Jonas Wixner, Intissar Anan

引用次数: 0

ELISA-4-amyloid: diagnostic accuracy of an ELISA panel for typing the four main types of systemic amyloidosis in subcutaneous abdominal fat tissue samples. ELISA-4-淀粉样蛋白：对腹部皮下脂肪组织样本中四种主要类型的系统性淀粉样变进行分型的 ELISA 面板诊断准确性。

IF 5.2 2区医学

Amyloid-Journal of Protein Folding Disorders Pub Date : 2024-08-06 DOI: 10.1080/13506129.2024.2385977

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":"Background: Reliable typing of amyloid is essential. Amyloid extraction from tissue enables immunochemical typing of the precursor protein using an enzyme-linked immunosorbent assay (ELISA).Objective: To assess the diagnostic accuracy of a panel of ELISAs for typing the four main types (AA, ATTR, AL-kappa and AL-lambda amyloid).Methods: 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.Results: 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%.Conclusions: 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.","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}

引用次数: 0