Computational investigation of the binding of a designed peptide to λ light chain amyloid fibril

2021 ◽  
Vol 23 (36) ◽  
pp. 20634-20644
Author(s):  
Zhenyu Wang ◽  
Wanying Huang ◽  
Manjun Liu ◽  
Stephen J Kennel ◽  
Jonathan S Wall ◽  
...  
Keyword(s):  
Light Chain ◽  
Amyloid Fibril ◽  
Computational Investigation ◽  
Binding Process ◽  
Lysine Residues ◽  
Λ Light Chain

Peptide P62 only binds to the canonical interface of the amyloid fibril. Lysine residues of P62 play an important role in the binding process by forming initial contacts with aspartic acids on the fibril surface.

scholarly journals Genetic pathogenesis of immunoglobulin light chain amyloidosis: basic characteristics and clinical applications

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Linchun Xu ◽  
Yongzhong Su
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Amyloid Fibril ◽  
Treatment Modalities ◽  
Driver Gene ◽  
Immunoglobulin Light Chain ◽  
Disease Evolution ◽  
Genetic Aberrations ◽  
Light Chain Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis

AbstractImmunoglobulin light chain amyloidosis (AL) is an indolent plasma cell disorder characterized by free immunoglobulin light chain (FLC) misfolding and amyloid fibril deposition. The cytogenetic pattern of AL shows profound similarity with that of other plasma cell disorders but harbors distinct features. AL can be classified into two primary subtypes: non-hyperdiploidy and hyperdiploidy. Non-hyperdiploidy usually involves immunoglobulin heavy chain translocations, and t(11;14) is the hallmark of this disease. T(11;14) is associated with low plasma cell count but high FLC level and displays distinct response outcomes to different treatment modalities. Hyperdiploidy is associated with plasmacytosis and subclone formation, and it generally confers a neutral or inferior prognostic outcome. Other chromosome abnormalities and driver gene mutations are considered as secondary cytogenetic aberrations that occur during disease evolution. These genetic aberrations contribute to the proliferation of plasma cells, which secrete excess FLC for amyloid deposition. Other genetic factors, such as specific usage of immunoglobulin light chain germline genes and light chain somatic mutations, also play an essential role in amyloid fibril deposition in AL. This paper will propose a framework of AL classification based on genetic aberrations and discuss the amyloid formation of AL from a genetic aspect.

A monoclonal antibody Hy20-54-16-3L to lambda (λ) light chain of human immunoglobulin reacts with amyloid in Alzheimer's disease brain

1990 ◽  
Vol 117 (1-2) ◽  
pp. 62-67 ◽  
Author(s):  
Fuyuki Kametani ◽  
Kikuko Tanaka ◽  
Maroto Sato ◽  
Seiichi Haga ◽  
Takashi Saitoh ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Monoclonal Antibody ◽  
Light Chain ◽  
Human Immunoglobulin ◽  
Λ Light Chain

Introduction of lysine residues on the light chain constant domain improves the labelling properties of a recombinant Fab fragment

1995 ◽  
Vol 8 (2) ◽  
pp. 185-191 ◽  
Author(s):  
Ari Hemminki ◽  
Anna-Marja Hoffrén ◽  
Kristiina Takkinen ◽  
Markus Vehniäinen ◽  
Maija-Liisa Mäkinen ◽  
...  
Keyword(s):  
Light Chain ◽  
Fab Fragment ◽  
Constant Domain ◽  
Lysine Residues

scholarly journals The Normal Counterpart of IgD Myeloma Cells in Germinal Center Displays Extensively Mutated IgVH Gene, Cμ–Cδ Switch, and λ Light Chain Expression

1998 ◽  
Vol 187 (8) ◽  
pp. 1169-1178 ◽  
Author(s):  
Christophe Arpin ◽  
Odette de Bouteiller ◽  
Diane Razanajaona ◽  
Isabelle Fugier-Vivier ◽  
Francine Brière ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Light Chain ◽  
Germinal Center ◽  
Plasma Cells ◽  
Precursor Cells ◽  
Memory B Cells ◽  
Hematopoietic Stem ◽  
Myeloma Cells ◽  
Λ Light Chain

Human myeloma are incurable hematologic cancers of immunoglobulin-secreting plasma cells in bone marrow. Although malignant plasma cells can be almost eradicated from the patient's bone marrow by chemotherapy, drug-resistant myeloma precursor cells persist in an apparently cryptic compartment. Controversy exists as to whether myeloma precursor cells are hematopoietic stem cells, pre–B cells, germinal center (GC) B cells, circulating memory cells, or plasma blasts. This situation reflects what has been a general problem in cancer research for years: how to compare a tumor with its normal counterpart. Although several studies have demonstrated somatically mutated immunoglobulin variable region genes in multiple myeloma, it is unclear if myeloma cells are derived from GCs or post-GC memory B cells. Immunoglobulin (Ig)D-secreting myeloma have two unique immunoglobulin features, including a biased λ light chain expression and a Cμ–Cδ isotype switch. Using surface markers, we have previously isolated a population of surface IgM−IgD+CD38+ GC B cells that carry the most impressive somatic mutation in their IgV genes. Here we show that this population of GC B cells displays the two molecular features of IgD-secreting myeloma cells: a biased λ light chain expression and a Cμ–Cδ isotype switch. The demonstration of these peculiar GC B cells to differentiate into IgD-secreting plasma cells but not memory B cells both in vivo and in vitro suggests that IgD-secreting plasma and myeloma cells are derived from GCs.

Amyloidosis: diagnosis and new therapies for a misunderstood and misdiagnosed disease

2019 ◽  
Vol 9 (6) ◽  
Author(s):  
Victoria E Thomas ◽  
Justin Smith ◽  
Merrill D Benson ◽  
Noel R Dasgupta
Keyword(s):  
Quality Of Life ◽  
Light Chain ◽  
Protein Identification ◽  
Amyloid Fibril ◽  
Immunoglobulin Light Chain ◽  
Transthyretin Amyloidosis ◽  
Identification Methods ◽  
Novel Treatments ◽  
Noninvasive Cardiac Imaging

Amyloidosis is a group of diseases characterized by extracellular deposition of amyloid fibril complexes. Fibril deposition results in organ dysfunction and possible failure. Amyloidosis is regarded as a rare disease, but in general is underdiagnosed. The two main types of systemic amyloidosis are immunoglobulin light chain and transthyretin amyloidosis. The increased availability of noninvasive cardiac imaging, genetic testing and improved laboratory assays and protein identification methods have led to increased diagnosis. However, in many cases, the diagnosis is not made until the patient develops organ impairment. Earlier diagnosis is required to prevent irreversible organ failure. Novel treatments for immunoglobulin light chain and transthyretin amyloidosis that halt disease progression, prolong and increase quality of life have recently become available.

scholarly journals Light chain type predicts organ involvement and survival in AL amyloidosis patients receiving stem cell transplantation

2018 ◽  
Vol 2 (7) ◽  
pp. 769-776 ◽  
Author(s):  
M Hasib Sidiqi ◽  
Mohammed A. Aljama ◽  
Eli Muchtar ◽  
Francis K. Buadi ◽  
Rahma Warsame ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Light Chain ◽  
Organ Involvement ◽  
Al Amyloidosis ◽  
Light Chain Type ◽  
Key Points ◽  
Λ Light Chain ◽  
Chain Type

Key Points λ Light chain AL amyloidosis is associated with a shorter PFS and OS compared with κ. Light chain type predicts likelihood of organ involvement in AL amyloidosis.

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