Article
Medicine, General & Internal
Emilia Czyzewska, Agnieszka Wisniewska, Anna Waszczuk-Gajda, Olga Ciepiela
Summary: The study indicates that the presence of monoclonal lambda chains in patients with AL amyloidosis may be associated with more severe damage to cardiomyocytes and dysfunction of the myocardium.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Immunology
Gemma Martinez-Rivas, Sebastien Bender, Christophe Sirac
Summary: Monoclonal immunoglobulin light chain amyloidosis is a rare but severe disease characterized by the deposition of amyloid fibrils in organs. The mechanisms and pathophysiology of this disease are still unclear. The development of reliable animal models for studying AL amyloidosis has proven to be challenging, hampering research efforts.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Puneet Rawat, R. Prabakaran, Sandeep Kumar, M. Michael Gromiha
Summary: A machine learning model has been developed to predict the amyloidogenic nature of antibody light chains with an accuracy of 79.7%, providing insights for prognosis improvement, understanding aggregation origins in antibody-based biotherapeutics, large-scale antibody sequence analysis, and rational engineering design.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Giovanni Palladini, Paolo Milani, Fabio Malavasi, Giampaolo Merlini
Summary: AL amyloidosis is caused by a small B cell clone producing toxic light chains, and the addition of daratumumab to standard treatment has shown promising results in increasing hematologic response rates and organ responses. Anti-CD38 antibodies like daratumumab offer new powerful tools for treating AL amyloidosis, potentially becoming new standards of care.
Review
Oncology
Linchun Xu, Yongzhong Su
Summary: Immunoglobulin light chain amyloidosis (AL) is a chronic plasma cell disorder characterized by FLC misfolding and amyloid deposition, classified into non-hyperdiploidy and hyperdiploidy subtypes with distinct treatment responses and prognostic outcomes based on cytogenetic patterns. Other genetic factors, such as specific immunoglobulin light chain germline genes and somatic mutations, also contribute to amyloid formation in AL.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2021)
Article
Immunology
Jipeng Yan, Jin Zhao, Xiaoxuan Ning, Yunlong Qin, Yan Xing, Yuwei Wang, Qing Jia, Boyong Huang, Rui Ma, Changhui Lei, Meilan Zhou, Zixian Yu, Yumeng Zhang, Wei-Feng Guo, Shiren Sun
Summary: This study demonstrates for the first time the alterations of gut microbiota in patients with AL amyloidosis and successfully establishes and validates a microbial-based diagnostic model. This provides a foundation for future research on microbe-based strategies for diagnosis and treatment in patients with AL amyloidosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Rebecca Sternke-Hoffmann, Thomas Pauly, Rasmus K. Norrild, Jan Hansen, Florian Tucholski, Magnus Haraldson Hoie, Paolo Marcatili, Mathieu Dupre, Magalie Duchateau, Martial Rey, Christian Malosse, Sabine Metzger, Amelie Boquoi, Florian Platten, Stefan U. Egelhaaf, Julia Chamot-Rooke, Roland Fenk, Luitgard Nagel-Steger, Rainer Haas, Alexander K. Buell
Summary: Researchers introduce a new systematic workflow for the biophysical characterization of multiple myeloma patient-derived immunoglobulin light chains (IgLCs) and find that in vivo aggregation behavior is unlikely to be linked to any single biophysical or biochemical parameter. They also discover that the potential to form amyloid fibrils is widespread in IgLC sequences and not limited to those sequences that form fibrils in patients.
Review
Biochemistry & Molecular Biology
Yukihiro Saito, Kazufumi Nakamura, Hiroshi Ito
Summary: Cardiac involvement significantly affects the prognosis of patients with systemic amyloidosis. Therapeutic methods have been developed for ATTR amyloidosis and AL amyloidosis, which show cardiac involvement, leading to improved prognosis. However, there is currently no established method for removing deposited amyloid, and further research is needed for protecting cardiovascular cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Alice Nevone, Maria Girelli, Silvia Mangiacavalli, Bruno Paiva, Paolo Milani, Pasquale Cascino, Maggie Piscitelli, Valentina Speranzini, Claudio Salvatore Cartia, Pietro Benvenuti, Ibai Goicoechea, Francesca Fazio, Marco Basset, Andrea Foli, Martina Nanci, Giulia Mazzini, Serena Caminito, Melania Antonietta Sesta, Simona Casarini, Paola Rognoni, Francesca Lavatelli, Maria Teresa Petrucci, Pier Paolo Olimpieri, Stefano Ricagno, Luca Arcaini, Giampaolo Merlini, Giovanni Palladini, Mario Nuvolone
Summary: A study has found that the N-glycosylation of amyloidogenic kappa LCs exhibits a distinctive sequence and spatial pattern, primarily located in the framework region 3 of the E strand, which may be associated with their pathogenic behavior.
Review
Oncology
Chunyan Sun, Xiaohong Wang, Renyi Zhang, Lingjie Xu, Bin Wang, Jian Li
Summary: This systematic review and meta-analysis investigated the efficacy and safety of intravenous daratumumab (DARA IV) for the treatment of amyloid light-chain (AL) amyloidosis. The results showed that DARA IV treatment had a good response rate and survival rate for patients.
CANCER CELL INTERNATIONAL
(2022)
Review
Oncology
Jose C. Martinez, Eben Lichtman
Summary: Immunoglobulin light chain amyloidosis can manifest as either systemic or localized forms. Localized amyloidosis, despite its lower incidence and heterogeneous clinical presentation, is associated with a good prognosis and a low risk of progressing to systemic disease. More sensitive techniques are needed at diagnosis to rule out systemic disease, and further research is needed to understand the cellular clonal evolution and molecular processes underlying localized amyloid formation.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Malte Johannes Hannich, Mohammed R. Abdullah, Kathrin Budde, Astrid Petersmann, Matthias Nauck, Alexander Dressel, Marie Suesse
Summary: This cohort study aimed to investigate whether further analysis of intrathecal inflammation can be omitted if the free light chain kappa (FLC kappa) quotient is within the reference range in the corresponding quotient diagram. The results showed that using FLC kappa-IF as a first line analysis can significantly reduce the workload of detecting immune responses in cerebrospinal fluid with high negative predictive value.
Article
Cardiac & Cardiovascular Systems
Candida Cristina Quarta, Jiexin Zheng, David Hutt, Simona F. Grigore, Richa Manwani, Sajitha Sachchithanantham, Shameem A. Mahmood, Carol J. Whelan, Marianna Fontana, Ana Martinez-Naharro, Liza Chacko, Helen J. Lachmann, Julian D. Gillmore, Claudio Rapezzi, Philip N. Hawkins, Ashutosh D. Wechalekar
Summary: Among AL CA patients, 39% had cardiac uptake of Tc-99m-DPD, with varying degrees. Those with cardiac uptake showed poorer cardiac function and higher NT-proBNP levels, and trended towards worse survival. Serial imaging showed a reduction in cardiac uptake in 23% of patients.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
(2021)
Review
Biochemistry & Molecular Biology
Nabil Belfeki, Nouha Ghriss, Mehran Monchi, Cyrus Moini
Summary: Cardiac amyloidosis is characterized by the accumulation of misfolded proteins in the heart. Transthyretin and light chain amyloidosis are the most common causes. Recent studies have shown an increasing incidence of this condition due to population aging and advancements in diagnostic tools.
Article
Biochemistry & Molecular Biology
Giulia Mazzini, Stefano Ricagno, Serena Caminito, Paola Rognoni, Paolo Milani, Mario Nuvolone, Marco Basset, Andrea Foli, Rosaria Russo, Giampaolo Merlini, Giovanni Palladini, Francesca Lavatelli
Summary: AL amyloidosis is characterized by the deposition of immunoglobulin light chains in target organs, with LC fragments consistently present in deposits. The fragmentation sites of LCs were found to be consistent across multiple organs but with some organ-specific positions, possibly due to a complex of proteases. Cleavage sites are concentrated in 'proteolysis-prone' regions, common to all tissues. Several proteolytic sites are not accessible on native dimers, while they are compatible with fibrils. This suggests that the heterogeneous ensemble of LC fragments originates in tissues and is consistent with digestion of preformed fibrils.
Article
Urology & Nephrology
Samih H. Nasr, Nelson Leung, Samar M. Said, Hassan B. Alkhateeb, Benjamin J. Madden, M. Cristine Charlesworth, Laurence H. Beck, Christopher P. Larsen, Sanjeev Sethi
Summary: Tubular basement membrane (TBM) deposits are rare in non-lupus membranous nephropathy, but have been observed in patients following allogeneic hematopoietic cell transplant. This distinctive clinicopathologic lesion is associated with chronic graft-versus-host disease (cGVHD) and is characterized by global subepithelial and extensive TBM immune complex deposits, along with acute tubular injury and tubulointerstitial inflammation. Treatment with prednisone and/or rituximab has shown to provide partial or complete remission.
AMERICAN JOURNAL OF KIDNEY DISEASES
(2022)
Article
Medicine, Research & Experimental
Jason N. Barreto, Joel M. Reid, Carrie A. Thompson, Kristin C. Mara, Andrew D. Rule, Kianoush B. Kashani, Nelson Leung, Thomas R. Larson, Renee M. McGovern, Thomas E. Witzig, Erin F. Barreto
Summary: This study evaluated the pharmacokinetics of high-dose methotrexate (HDMTX) in adult lymphoma patients, finding that the cystatin C-based eGFR equation best predicted MTX clearance and highlighting the high interpatient variability in HDMTX pharmacokinetics.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Oncology
Moritz Binder, Bharat Nandakumar, S. Vincent Rajkumar, Prashant Kapoor, Francis K. Buadi, David Dingli, Martha Q. Lacy, Morie A. Gertz, Suzanne R. Hayman, Nelson Leung, Amie Fonder, Miriam Hobbs, Yi Lisa Hwa, Eli Muchtar, Rahma Warsame, Taxiarchis Kourelis, Wilson Gonsalves, Stephen Russell, Yi Lin, Mustaqeem Siddiqui, Robert A. Kyle, Angela Dispenzieri, Shaji K. Kumar
Summary: Recent advancements in disease biology, drug development, and supportive care have led to improved outcomes in multiple myeloma patients. However, disparities exist in mortality trends among patient populations, with older patients and those with unfavorable disease characteristics experiencing higher excess mortality. Efforts should be made to develop safe and effective therapies for these vulnerable patients and to ensure timely access to specialized care in the community.
Article
Hematology
Joselle Cook, Kah-Whye Peng, Thomas E. Witzig, Stephen M. Broski, Jose C. Villasboas, Jonas Paludo, Mrinal Patnaik, Vincent Rajkumar, Angela Dispenzieri, Nelson Leung, Francis Buadi, Nora Bennani, Stephen M. Ansell, Lianwen Zhang, Nandakumar Packiriswamy, Baskar Balakrishnan, Bethany Brunton, Marissa Giers, Brenda Ginos, Amylou C. Dueck, Susan Geyer, Morie A. Gertz, Rahma Warsame, Ronald S. Go, Suzanne R. Hayman, David Dingli, Shaji Kumar, Leif Bergsagel, Javier L. Munoz, Wilson Gonsalves, Taxiarchis Kourelis, Eli Muchtar, Prashant Kapoor, Robert A. Kyle, Yi Lin, Mustaqeem Siddiqui, Amie Fonder, Miriam Hobbs, Lisa Hwa, Shruthi Naik, Stephen J. Russell, Martha Q. Lacy
Summary: This study investigated the safety and efficacy of intravenous oncolytic virotherapy in patients with relapsed/refractory hematologic malignancies. The results showed that VSV-IFN beta-NIS had significant therapeutic effects in patients with TCL, possibly through a combination of oncolytic tumor destruction and immune response.
Article
Oncology
Samer K. Khaled, Kathleen Claes, Yeow Tee Goh, Yok Lam Kwong, Nelson Leung, Wlodzimierz Mendrek, Ryotaro Nakamura, Jameela Sathar, Edmund Ng, Narinder Nangia, Steve Whitaker, Alessandro Rambaldi
Summary: This study evaluated the safety and efficacy of Narsoplimab in adults with HSCT-TMA, and the results showed significant improvements in laboratory TMA markers, clinical response, and overall survival.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Urology & Nephrology
Sanjeev Sethi, Benjamin Madden, Marta Casal Moura, Samih H. Nasr, Nattawat Klomjit, LouAnn Gross, Vivian Negron, M. Cristine Charlesworth, Mariam P. Alexander, Nelson Leung, Ulrich Specks, Fernando C. Fervenza, Mark Haas
Summary: In this study, a novel antigen associated with membranous nephropathy (MN) in patients receiving hematopoietic stem cell transplant (HSCT) was identified using laser microdissection and tandem mass spectrometry (MS/MS). The antigen, called FAT1, was detected in the glomeruli of patients with PLA2R-negative MN. Further studies confirmed the presence of FAT1-associated MN in a majority of HSCT-related MN cases. This study provides valuable insights into the pathogenesis of MN in HSCT patients and may contribute to the development of targeted therapies.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Letter
Urology & Nephrology
Frank Bridoux, Nelson Leung, Jean Paul Fermand
KIDNEY INTERNATIONAL
(2022)
Article
Hematology
Aldo A. Acosta-Medina, Ann M. Moyer, Ronald S. Go, Maria Alice V. Willrich, Fernando C. Fervenza, Nelson Leung, Christianne Bourlon, Jeffrey L. Winters, Grant M. Spears, Sandra C. Bryant, Meera Sridharan
Summary: Eculizumab is effective for complement-mediated thrombotic microangiopathy. Discontinuation of therapy does not universally lead to relapse. This study aimed to assess the role of complement genetic variants in predicting recurrence after Eculizumab withdrawal. A total of 280 patients were included, with CFH and MCP/CD46 being the most commonly identified genetic variants. The relapse rate after discontinuation was 29.6%, with CFH and MCP/CD46 variants in canonical splice regions having the highest relapse rates.
Letter
Urology & Nephrology
Jason N. Barreto, Kianoush B. Kashani, Kristin C. Mara, Andrew D. Rule, John C. Lieske, Callen D. Giesen, Carrie A. Thompson, Nelson Leung, Thomas E. Witzig, Erin F. Barreto
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Urology & Nephrology
Naba Farooqui, Mark Zaidi, Lisa Vaughan, Trevor D. McKee, Eram Ahsan, Kevin D. Pavelko, Jose C. Villasboas, Svetomir Markovic, Timucin Taner, Nelson Leung, Haidong Dong, Mariam P. Alexander, Sandra M. Herrmann
Summary: This study found that immune checkpoint inhibitors (ICIs) therapy may lead to acute kidney injury (AKI) and there are no biomarkers currently available to distinguish AKI caused by ICIs from other causes. The urine levels of cytokines such as TNF-a, IL-2, and IL-10 were significantly higher in AKI-ICI patients. Therefore, these T-cell responses and their respective cytokines may be helpful in differentiating AKI-ICI from AKI-other.
KIDNEY INTERNATIONAL REPORTS
(2023)
Letter
Hematology
Nate Gipe, Nelson Leung, Terra Lasho, Abhishek Mangaonkar, Hassan Alkhateeb, Aref Al-Kali, Naseema Gangat, William Hogan, Kristen McCullough, Ayalew Tefferi, Mariam Priya Alexander, Mrinal M. Patnaik
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Oncology
Nelson Leung, S. Vincent Rajkumar
Summary: Light chain cast nephropathy (LCCN) is a significant cause of acute kidney injury (AKI) in patients with multiple myeloma (MM) and is now considered as a defining event of myeloma. While long-term prognosis has improved, short-term mortality remains higher in patients with LCCN if renal failure is not reversed. Rapid reduction of involved serum free light chain is critical for renal function recovery. Treatment algorithm for MM patients with biopsy-proven LCCN or ruling out other causes of AKI is provided based on randomized trial data whenever available. Clinical trial enrollment is recommended prior to following the treatment algorithm.
BLOOD CANCER JOURNAL
(2023)
Editorial Material
Urology & Nephrology
Sheron Latcha, Nelson Leung
Review
Immunology
Hans-Joachim Anders, A. Richard Kitching, Nelson Leung, Paola Romagnani
Summary: 'Glomerulonephritis' (GN) refers to a group of immune-mediated disorders characterized by inflammation of the kidney's filtration units. Current classification is based on histopathological lesion patterns, but these patterns do not align well with the diverse pathological mechanisms and do not guide optimal therapy. Instead, a proposed immunopathogenesis-based classification groups GN disorders into five categories, allowing for more targeted and effective treatments.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Urology & Nephrology
Jason N. Barreto, Erin F. Barreto, Kristin C. Mara, Andrew D. Rule, John C. Lieske, Callen D. Giesen, Carrie A. Thompson, Nelson Leung, Thomas E. Witzig, Kianoush B. Kashani