Structural Studies of the Variable Region of Immunoglobulin Light-Chain-Type Amyloid Fibril Proteins

Amyloidosis ◽  
1986 ◽  
pp. 463-475 ◽  
Author(s):  
Knut Sletten ◽  
Per Westermark ◽  
Gunnar Husby
Keyword(s):  
Light Chain ◽  
Amyloid Fibril ◽  
Variable Region ◽  
Structural Studies ◽  
Immunoglobulin Light Chain ◽  
Light Chain Type ◽  
Chain Type

scholarly journals The complete amino acid sequence of a prototype immunoglobulin-λ light-chain-type amyloid-fibril protein AR

1981 ◽  
Vol 195 (3) ◽  
pp. 561-572 ◽  
Author(s):  
K Sletten ◽  
J B Natvig ◽  
G Husby ◽  
J Juul
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Light Chain ◽  
Amyloid Fibril ◽  
Variable Region ◽  
Amino Acid Residues ◽  
Variable Regions ◽  
Light Chain Type ◽  
Amyloid Fibril Protein ◽  
Chain Type

The amino acid sequence of an amyloid-fibril protein of immunoglobulin light-chain type (AL) was elucidated. The sequence determination involved digesting the protein with trypsin, thermolysin and pepsin. The protein was found to consist of 154 amino acid residues and is thus missing about half of the constant region of a light chain. A certain heterogeneity in the length of the polypeptide was observed in the C-terminal region. The amino acid sequence from CDR (complementary-determining region) 1 and FR (framework region) 3 indicated an oligoclonal origin of the protein. By comparing the primary structure of protein AR with other lambda- and even kappa-chains, it was revealed that protein AR had an insertion of two residues of aspartic acid, namely residues 68 and 69, which has not been reported previously in light chains. The overall sequence homology in the variable region showed that protein AR is more similar to V lambda V than to the other subgroups [Kabat, Wu & Bilofsky (1979) Variable regions of Immunoglobulin Chains, Medical Computer Systems, Bolt, Beranek and Newman, Cambridge, MA].

scholarly journals Structural studies of a carbohydrate-containing immunoglobulin-λ-light-chain amyloid-fibril protein (AL) of variable subgroup III

1986 ◽  
Vol 239 (3) ◽  
pp. 545-551 ◽  
Author(s):  
E Holm ◽  
K Sletten ◽  
G Husby
Keyword(s):  
Amino Acid ◽  
Light Chain ◽  
Amyloid Fibril ◽  
Gel Filtration ◽  
Hypervariable Region ◽  
Variable Region ◽  
Amino Acid Residues ◽  
Immunoglobulin Light Chain ◽  
Amyloid Fibril Protein ◽  
Chain Type

The amino acid sequence of the variable region of a carbohydrate-containing amyloid-fibril protein MOL of immunoglobulin-light-chain type (AL) was elucidated. The sequence determination involved cleaving the protein with CNBr, BNPS-skatole, thermolysin and trypsin. The sequenced protein consisted of about 130 amino acid residues; however, gel-filtration and N-terminal analysis studies revealed AL proteins ranging in Mr from about 10,000 to 25,000. The oligosaccharide chain was found to be bound in the hypervariable region. By sequence homology to other lambda chains the AL protein MOL was shown to be of the V lambda III subgroup.

Immunoglobulin light-chain type in Sjögren's syndrome

1983 ◽  
Vol 14 (4) ◽  
pp. 380
Author(s):  
Guillermo J. Ruiz-Argüelles ◽  
Efraín Díaz-Jouanen ◽  
Donato Alarcó-Segovia
Keyword(s):  
Sjögren’S Syndrome ◽  
Light Chain ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Immunoglobulin Light Chain ◽  
Light Chain Type ◽  
Chain Type ◽  
Sjögren‘S Syndrome

scholarly journals NEW, THIRD CLASS OF AMYLOID FIBRIL PROTEIN

1974 ◽  
Vol 139 (3) ◽  
pp. 773-778 ◽  
Author(s):  
G. Husby ◽  
J. B. Natvig ◽  
K. Sletten
Keyword(s):  
Light Chain ◽  
Amyloid Fibril ◽  
Variable Region ◽  
Primary Amyloidosis ◽  
Amyloid Proteins ◽  
Immunoglobulin Light Chain ◽  
Structural Identity ◽  
Amyloid Fibril Protein

An unusual protein AR was isolated from the amyloid fibril preparation derived from a patient with primary amyloidosis. Protein AR was unique in its antigenicity, and revealed no structural identity with any known amyloid proteins or with immunoglobulin chains or fragments. Thus a new third class of amyloid fibril proteins besides the immunoglobulin light-chain variable region fragments and the nonimmunoglobulin protein AS, has been characterized. A component antigenically related to protein AR was found in the serum of the patient.

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.

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.

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