Amyloidogenic proteins and occurrence of different amyloidosis in different animal species

Amyloidosis is a poly-systemic disease caused by extracellular deposition of biologically inactive amyloid proteins, most often in kidneys, liver, nervous system, thyroid, spleen and heart. Depending on the site of production and deposition they can be classified into causing localised (organ-limited) and systemic amyloidosis. Disturbances in functioning of individual organs occur with an increase of the amount of accumulated protein what in turn may lead to the death of the affected individual. The occurrence of amyloidosis has been reported in human, but in animals, the most common form is AA amyloidosis, while AL amyloidosis is the least common. Due to the fact that symptoms of amyloidosis vary and often resemble those occurring in the course of other diseases, it is difficult to diagnose. Treatment of amyloidosis is aimed at improving functioning of the affected organs, yet the disease is incurable.

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Dysautonomias in amyloidosis

Nervenheilkunde ◽

10.1055/s-0038-1628501 ◽

2013 ◽

Vol 32 (04) ◽

pp. 192-196

Author(s):

B. P. C. Hazenberg

Keyword(s):

Cell Clone ◽

Early Stage ◽

Systemic Disease ◽

Interdisciplinary Approach ◽

Signs And Symptoms ◽

Systemic Amyloidosis ◽

Al Amyloidosis ◽

Life Threatening ◽

The Individual ◽

Common Manifestation

SummarySystemic amyloidosis is a life-threatening and frequently unrecognized cause of dysautonomia. Autonomic neuropathy is a common manifestation of AL amyloidosis (caused by deposition of an immunoglobulin free light chain produced by an underlying plasma cell clone) and of autosomal dominant hereditary ATTR amyloidosis (caused by a transthyretin mutation). The following review aims to alert clinicians to look out for signs and symptoms of amyloidosis to enable the bioptic diagnosis at an early stage. Suspicion of systemic amyloidosis is usually raised by the systemic, multi-organ character of the disease. An interdisciplinary approach is needed in the individual patient in order to establish the diagnosis and to obtain a clear overview of the actual multitude of organ problems. This overview is necessary for risk management and for making a well-considered treatment choice. Collaboration of all medical specialists involved is necessary to deliver optimal treatment and care to the patient with this systemic disease.

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Valuation of MCP-1 and VEGF Chemokines In Serum of Patients with AL Amyloidosis

Blood ◽

10.1182/blood.v116.21.1922.1922 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1922-1922

Author(s):

Alessandro Moscetti ◽

Francesca Saltarelli ◽

Maria Paola Bianchi ◽

Guglielmo Bruno ◽

Gerardo Salerno ◽

...

Keyword(s):

Bone Marrow ◽

Inflammatory Process ◽

Conflicts Of Interest ◽

Systemic Disease ◽

Inflammatory Cells ◽

Mononuclear Phagocytes ◽

Systemic Amyloidosis ◽

Light Chains ◽

Al Amyloidosis ◽

Localized Amyloidosis

Abstract Abstract 1922 AL amyloidosis is a pathology characterised by the deposition of fibrillary aggregates of immunoglobuline light chains with β-sheet conformation. The light chains are synthetized by neoplastic plasma cell and fibrils deposition can infiltrate tissues leading to multi systemic organ damage. To evaluate if vascular modifications are involved in AL amyloidosis, inflammatory activity of cytokines as MCP-1 and VEGF was investigated. MCP-1 is a chemokine that activates mononuclear phagocytes by promoting leukocyte-endothelium binding and migration to sites of inflammation, while VEGF is an endothelial cell mitogen and permeability factor that is potently angiogenic in bone marrow of AL amyloidosis patients. Aim of this study is to evaluate serum cytokines MCP-1 and VEGF levels in patients with systemic or localized AL amyloidosis at presentation to find out potential differences useful to define a characteristic inflammatory pattern. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis and analyzed for serum MCP-1 and VEGF levels. Mann-Whitney test and Spearman correlation were used to compare results. MCP-1 level was significantly higher in the serum of patients with systemic disease (350.52±58.70 pg/ml) compared to the group of patients with localized amyloidosis (147.82±26.03; p=0.004); VEGF was also significantly increased in systemic disease group (p= 0.028). In addition, a positive correlation between MCP-1 and VEGF (r2= 0.755; p=0.031) has been found in the group of patients with systemic amyloidosis. Results seems to suggest a difference in serum cytokine MCP-1 and VEGF levels between AL systemic and localized amyloidosis. In systemic amyloidosis the neoplastic plasma cells interact with bone marrow microenvironment resulting in VEGF release leading to a new angiogenesis also supported by an inflammatory cells increase. The MCP-1 activates and promotes leukocyte-endothelium binding increasing the inflammatory process. The high correlation between MCP-1 and VEGF suggests a positive relationship between a new angiogenesis and a migration of inflammatory cells in the bone marrow stroma. On the basis of our results, MCP-1 and VEGF chemokines can be used to evaluate the inflammatory process in patient with systemic or localized AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

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Heart Function In Systemic and Localized AL Amyloidosis: Role of NT-ProBNP and MPC-1

Blood ◽

10.1182/blood.v116.21.5006.5006 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5006-5006

Author(s):

Francesca Saltarelli ◽

Alessandro Moscetti ◽

Guglielmo Bruno ◽

Bruno Monarca ◽

Gerardo Salerno ◽

...

Keyword(s):

Conflicts Of Interest ◽

Heart Function ◽

Systemic Disease ◽

Plasma Concentrations ◽

Serum Levels ◽

Mononuclear Phagocytes ◽

Systemic Amyloidosis ◽

Al Amyloidosis ◽

Heart Involvement ◽

Localized Amyloidosis

Abstract Abstract 5006 In AL amyloidosis typical sites of amyloid buildup are heart, skin, gastrointestinal tract, liver, kidneys, and blood vessels. To evaluate the heart involvement in systemic and localized amyloidosis proBNP, peptide (NT-proBNP; 76 amino acids) and MPC-1 were investigated. NT-proBNP have been described as useful marker for the diagnosis heart disease, and its plasma concentrations correlate with the functional classification of patients according to the New York Heart Association (NYHA). MCP-1 is a chemokine that activates mononuclear phagocytes by promoting leukocyte–endothelium binding and migration to sites of inflammation. The MCP-1 levels seem to be related to the severity of cardiac alteration, as demonstrated by the coronary angiogram. NT-proBNP and MPC-1 serum levels were performed in systemic or localized AL amyloidosis to evaluate if there was a difference in the heart involvement. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. To analyze the results of NT-proBNP and MPC-1, Mann-Whitney test was performed. NT-proBNP serum values were significantly (p=0.007) increased in systemic disease. Also, MPC-1 serum levels were significantly (p=0.004) higher in the patients with systemic disease (350.52±58.70 pg/ml) if compared to the group of localized amyloidosis (147.82±26.03 pg/ml). On the basis of our results, the heart seem to be functionally more involved in AL systemic amyloidosis than in localized disease, as demonstrated by the higher NT-proBNP and MPC-1 serum values. Disclosures: No relevant conflicts of interest to declare.

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IL-4 and IL-1 Serum Levels In Systemic and Localized Amyloidosis

Blood ◽

10.1182/blood.v116.21.5000.5000 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5000-5000

Author(s):

Alessandro Moscetti ◽

Francesca Saltarelli ◽

Guglielmo Bruno ◽

Bruno Monarca ◽

Gerardo Salerno ◽

...

Keyword(s):

Inflammatory Response ◽

Conflicts Of Interest ◽

Systemic Disease ◽

Inverse Correlation ◽

Serum Levels ◽

Systemic Amyloidosis ◽

Al Amyloidosis ◽

Th2 Response ◽

Localized Amyloidosis ◽

Localized Disease

Abstract Abstract 5000 AL amyloidosis is a plasmacellular discrasia characterized by the deposition of light chains fibrils that infiltrate tissues leading to multisystemic organ involvement. Amyloidosis can be systemic or localized disease. No immunological markers are avaibable to distinguish the systemic from localized disease. IL-4 and IL-1 cytokines were performed to evaluate if there is a different inflammatory pattern between the two clinical forms. IL-4 is the central regulator of T helper 2 (Th2) immune responses, with also a major impact on innate immune cells. IL-1 is produced by macrophages, monocytes, fibroblasts and dendritic cells which play an important role in the inflammatory response, activating the Th1-mediated IL2 release. IL-1 increases the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes to sites of infection. The study was devoted to evaluate serum levels of IL-4 and IL-1 in systemic or localized AL amyloidosis at presentation and to find out potential Th1 and Th2 disequilibrium. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. Serum IL-4 and IL-1 levels were detected. Mann-Whitney test and correlation test were used to analyze results. IL-4 level was significantly (p < 0.05) higher in patients with localized disease compared to the group with systemic amyloidosis. IL-1 was instead significantly (p < 0.01) increased in systemic disease. In this, an inverse correlation between IL-4 and IL-1a was found (r2= –0.707; p = 0.05). In systemic amyloidosis, the regulatory mechanism of Th1/Th2 response was polarized versus Th1, as demonstrated by low serum level of IL-4 and high level of IL-1. The negative correlation between serum IL-4 and IL-1 levels demonstrates a disregulation of the immune system in systemic disease as supported by the increased activity of Th1. The results seem to hypothesize that IL-4 could be able to antagonize the diffusion of disease, as demonstrated by the higher IL-4 serum levels in localized amyloidosis. So IL-4 and IL-1 can be considered sensible markers for the inflammatory response assessment both in systemic and localized amyloidosis. Disclosures: No relevant conflicts of interest to declare.

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Scalp biopsy identifies systemic amyloidosis presenting as isolated telogen effluvium: A case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x19847783 ◽

2019 ◽

Vol 7 ◽

pp. 2050313X1984778

Author(s):

Rory A Sutherland ◽

Richard I Crawford

Keyword(s):

Multiple Myeloma ◽

Rare Case ◽

Systemic Disease ◽

Antibody Fragments ◽

Systemic Amyloidosis ◽

Plasma Cell Dyscrasia ◽

Al Amyloidosis ◽

Biopsy Finding ◽

Scalp Biopsy ◽

Underlying Pathology

AL amyloidosis is a complication of B-cell dyscrasias and multiple myeloma, manifest as deposition of antibody fragments in many different organs, including the skin. We describe a rare case of this systemic disease which presented with isolated scalp alopecia. Further investigation led to the diagnosis of an occult plasma-cell dyscrasia, showing the benefit of including systemic amyloidosis in the differential diagnosis of alopecia. The biopsy finding of cutaneous amyloidosis should prompt further workup to exclude an underlying pathology.

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NT-ProBNP and VEGF Serum Evaluation In AL Amyloidosis

Blood ◽

10.1182/blood.v116.21.5008.5008 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5008-5008

Author(s):

Francesca Saltarelli ◽

Alessandro Moscetti ◽

Maria Paola Bianchi ◽

Guglielmo Bruno ◽

Gerardo Salerno ◽

...

Keyword(s):

Cardiac Involvement ◽

Conflicts Of Interest ◽

Vascular Endothelial Cells ◽

Systemic Disease ◽

Serum Levels ◽

Systemic Amyloidosis ◽

The Other ◽

Al Amyloidosis ◽

Vascular Endothelial ◽

Heart Dysfunction

Abstract Abstract 5008 AL amyloidosis is a plasmacellular dyscrasia in which fibrillary deposits containing monoclonal immunoglobuline light chains infiltrate tissues causing their dysfunction and failure. Amyloidosis could be classified into rare localized or more frequent systemic forms such as AL amyloidosis. Cardiac dysfunction is a very frequent feature in AL amyloidosis patients. To evaluate heart involvement both in systemic and localized AL amyloidosis, serum levels of pro-BNP (peptide NT-proBNP; 76 amino acids) and VEGF were investigated. NT-proBNP has been described as an useful marker for heart dysfunction and its role as a prognostic factor for patients with systemic AL amyloidosis has been validated. VEGF is a signaling protein that stimulates new blood vessel formation and showed to be a mitogen for vascular endothelial cells. Serum NT-proBNP and VEGF levels were performed in systemic or localized AL amyloidosis patients to evaluate if there is any correlation between them. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. To analyze the results of NT-proBnp and VEGF, Mann-Whitney test and Spearman correlation were performed. Serum NT-proBNP values were significantly increased in systemic disease (p=0.004). VEGF serum levels were also significantly higher in patients with systemic disease compared to the other group (p=0.027). No significant correlation between NT-proBNP and VEGF levels was found. We know that proBNP levels are significantly increased in patients with systemic amyloidosis and cardiac involvement. On the other hand, VEGF serum levels resulted to be increased in systemic disease. Nevertheless, on the basis of our results, we found absence of a significant correlation between NT-proBNP and VEGF increases. In our opinion, such finding could suggest that VEGF based neoangiogenesis is not significantly involved in AL amyloidosis heart dysfunction. Disclosures: No relevant conflicts of interest to declare.

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Detergent properties as the basis of the dimexide therapeutic effect in AA-amyloidosis infectious nature (clinical case analysis)

Nephrology (Saint-Petersburg) ◽

10.36485/1561-6274-2020-24-2-60-71 ◽

2020 ◽

Vol 24 (2) ◽

pp. 60-71

Author(s):

V. Rameev ◽

L. Kozlovskaya ◽

A. Rameeva ◽

P. Tao

Keyword(s):

Therapeutic Effect ◽

Medical Practice ◽

Clinical Case ◽

Clinical Observation ◽

Case Analysis ◽

Systemic Amyloidosis ◽

Aa Amyloidosis ◽

Functional Amyloid ◽

History Of

The article discusses the current possibilities of postinfectious AA-amyloidosis treatment with dimexide on the example of clinical observation, discribes in detail the problem of functional amyloid and debates the prospects of the principle of amyloid resorption in the treatment of systemic amyloidosis. The history of the use of dimexide in medical practice is given, thenecessary dataon the pharmacology of dimexide are presented.

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Aggregation of Mouse Serum Amyloid A Protein Was Promoted by Amyloid-Enhancing Factors with the More Genetically Homologous Serum Amyloid A

International Journal of Molecular Sciences ◽

10.3390/ijms22031036 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1036

Author(s):

Xuguang Lin ◽

Kenichi Watanabe ◽

Masahiro Kuragano ◽

Kiyotaka Tokuraku

Keyword(s):

Amino Acid ◽

Serum Amyloid A ◽

Animal Species ◽

Amino Acid Sequences ◽

Serum Amyloid ◽

Mouse Serum ◽

Aa Amyloidosis ◽

Basic Residue ◽

Amyloid A ◽

Serum Amyloid A Protein

Amyloid A (AA) amyloidosis is a condition in which amyloid fibrils characterized by a linear morphology and a cross-β structure accumulate and are deposited extracellularly in organs, resulting in chronic inflammatory diseases and infections. The incidence of AA amyloidosis is high in humans and several animal species. Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis. Amyloid enhancing factor (AEF) serves as a seed for fibril formation and shortens the onset of AA amyloidosis sharply. In this study, we examined whether AEFs extracted and purified from five animal species (camel, cat, cattle, goat, and mouse) could promote mouse SAA (mSAA) protein aggregation in vitro using quantum-dot (QD) nanoprobes to visualize the aggregation. The results showed that AEFs shortened and promoted mSAA aggregation. In addition, mouse and cat AEFs showed higher mSAA aggregation-promoting activity than the camel, cattle, and goat AEFs. Interestingly, homology analysis of SAA in these five animal species revealed a more similar amino acid sequence homology between mouse and cat than between other animal species. Furthermore, a detailed comparison of amino acid sequences suggested that it was important to mSAA aggregation-promoting activity that the 48th amino acid was a basic residue (Lys) and the 125th amino acid was an acidic residue (Asp or Glu). These data imply that AA amyloidosis exhibits higher transmission activity among animals carrying genetically homologous SAA gene, and may provide a new understanding of the pathogenesis of amyloidosis.

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