Spontaneous, Experimentally Induced, and Transmissible AA Amyloidosis in Japanese Quail (Coturnix japonica)

The authors describe a spontaneous case of amyloid A (AA) amyloidosis in an adult female Japanese quail ( Coturnix japonica). The bird developed AA amyloidosis secondary to chronic peritonitis caused by a Gram-negative bacillus infection. Mild amyloid deposition was also identified in the intestinal tract of apparently healthy adult individuals, suggesting that quail may develop intestinal amyloidosis with age. Based on these observations, it was hypothesized that quail can develop AA amyloidosis following inflammatory stimulation with lipopolysaccharide (LPS). Therefore, adult quail were repeatedly injected with LPS and the development of AA amyloidosis was confirmed. The amyloid deposition in this model increased when quail amyloid was intravenously injected as an amyloid-enhancing factor. The experiments were repeated with young quail, but amyloid deposits were not observed following LPS injections. However, AA amyloidosis did develop when quail amyloid was injected in addition to LPS. These results indicated that adult quail develop AA amyloidosis after inflammatory stimulation with LPS. Furthermore, quail AA amyloidosis was shown to have transmissibility regardless of age. Interestingly, the authors found that administration of chicken amyloid fibrils also induced AA amyloidosis in young quail. This is the first report of cross-species transmission of avian AA amyloidosis.

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Deposition, Clearance, and Reinduction of Amyloid A Amyloid in Interleukin 1 Receptor Antagonist Knockout Mice

Veterinary Pathology ◽

10.1177/0300985816658772 ◽

2016 ◽

Vol 54 (1) ◽

pp. 99-110 ◽

Cited By ~ 4

Author(s):

K. Watanabe ◽

K. Uchida ◽

J. K. Chambers ◽

N. Ushio ◽

H. Nakayama

Keyword(s):

Receptor Antagonist ◽

Knockout Mice ◽

Interleukin 1 ◽

Recovery Process ◽

Amyloid Deposition ◽

Aa Amyloidosis ◽

Amyloid A ◽

Enhancing Factor ◽

Amyloid Deposits ◽

Amyloid Enhancing Factor

Amyloid A (AA) amyloidosis is characterized by the extracellular deposition of AA amyloid and results in the irreversible dysfunction of parenchymal organs. In experimental models, AA amyloid deposits are cleared following a decrease in circulating serum amyloid A (SAA) concentrations. Additional inflammatory stimuli during this recovery process may induce more severe amyloid redeposition. In the present study, we confirmed the deposition, clearance, and reinduction of AA amyloid deposits in interleukin 1 receptor antagonist knockout mice (IL-1raKO) and studied the SAA levels and amyloid-enhancing factor activity based on the time-dependent changes of amyloid deposition. Histopathologically, following initial (day 0) injection of amyloid-enhancing factor in combination with an inflammatory stimulus (silver nitrate [AgNO3]), amyloid deposition peaked by day 20, and its deposition gradually decreased after day 35. SAA concentrations in serum were precipitously elevated on day 1 but returned to normal levels by day 10, whereas the SAA dimer was detected in serum after day 45. An additional AgNO3 injection was administered to mice with amyloidosis on day 5, 10, 35, or 50, and all mice developed large amyloid deposits. Amyloid deposition was most severe in mice treated with AgNO3 on day 35. The inoculation of sera from mice with AA amyloidosis, combined with AgNO3, induced AA amyloidosis. Serum samples collected on days 35 and 50, which contained high concentrations of the SAA dimer, induced amyloidosis in a high proportion (83%) of mice. Therefore, increased SAA and/or its dimer in serum during the recovery process may markedly exacerbate the development of AA amyloidosis.

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Colocalization of Apolipoprotein AI in Various Kinds of Systemic Amyloidosis

Journal of Histochemistry & Cytochemistry ◽

10.1369/jhc.4a6387.2005 ◽

2005 ◽

Vol 53 (2) ◽

pp. 237-242 ◽

Cited By ~ 10

Author(s):

Naohiro Sakata ◽

Yoshinobu Hoshii ◽

Tomomi Nakamura ◽

Makiko Kiyama ◽

Hirofumi Arai ◽

...

Keyword(s):

Transgenic Mice ◽

Amyloid Fibrils ◽

Senile Plaques ◽

Systemic Amyloidosis ◽

High Density Lipoproteins ◽

Apolipoprotein Ai ◽

Aa Amyloidosis ◽

Amyloid A ◽

Amyloid Deposits ◽

A Minor

Apolipoprotein AI (apoAI), a major component of high-density lipoproteins, is one of the major amyloid fibril proteins and a minor constituent of the senile plaques observed in Alzheimer's disease. We examined colocalization of apoAI in various kinds of systemic amyloidosis in this study. Forty-three of 48 formalin-fixed paraffin-embedded heart specimens with various forms of systemic amyloidosis reacted immunohistochemically with anti-human apoAI antibody. ApoAI was also detected in water-extracted amyloid material by immunoblotting. In addition, we observed colocalization of apoAI and murine amyloid A (AA) amyloidosis in human apoAI transgenic mice. This is the first report of colocalization of apoAI with amyloid deposits in various forms of human systemic amyloidosis and murine AA amyloidosis in human apoAI transgenic mice. ApoAI may not always be a major component of amyloid fibrils, even when it is present in systemic amyloid deposits.

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Identification of a Unique Amyloid Sequence in AA Amyloidosis of a Pig Associated With Streptococcus Suis Infection

Veterinary Pathology ◽

10.1177/0300985816653792 ◽

2016 ◽

Vol 54 (1) ◽

pp. 111-118 ◽

Cited By ~ 4

Author(s):

J. Kamiie ◽

G. Sugahara ◽

S. Yoshimoto ◽

N. Aihara ◽

T. Mineshige ◽

...

Keyword(s):

Amyloid Fibrils ◽

Streptococcus Suis ◽

Peptide Sequence ◽

Spectrometric Analysis ◽

Aa Amyloidosis ◽

Amyloid A ◽

Amyloid Deposits ◽

N Terminus ◽

Seeding Polymerization

Here we report a pig with amyloid A (AA) amyloidosis associated with Streptococcus suis infection and identification of a unique amyloid sequence in the amyloid deposits in the tissue. Tissues from the 180-day-old underdeveloped pig contained foci of necrosis and suppurative inflammation associated with S. suis infection. Congo red stain, immunohistochemistry, and electron microscopy revealed intense AA deposition in the spleen and renal glomeruli. Mass spectrometric analysis of amyloid material extracted from the spleen showed serum AA 2 (SAA2) peptide as well as a unique peptide sequence previously reported in a pig with AA amyloidosis. The common detection of the unique amyloid sequence in the current and past cases of AA amyloidosis in pigs suggests that this amyloid sequence might play a key role in the development of porcine AA amyloidosis. An in vitro fibrillation assay demonstrated that the unique AA peptide formed typically rigid, long amyloid fibrils (10 nm wide) and the N-terminus peptide of SAA2 formed zigzagged, short fibers (7 nm wide). Moreover, the SAA2 peptide formed long, rigid amyloid fibrils in the presence of sonicated amyloid fibrils formed by the unique AA peptide. These findings indicate that the N-terminus of SAA2 as well as the AA peptide mediate the development of AA amyloidosis in pigs via cross-seeding polymerization.

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Generalized AA-amyloidosis in Siberian Tigers (Panthera tigris altaica) with Predominant Renal Medullary Amyloid Deposition

Veterinary Pathology ◽

10.1177/030098589803500108 ◽

1998 ◽

Vol 35 (1) ◽

pp. 70-74 ◽

Cited By ~ 11

Author(s):

C. Schulze ◽

M. Brügmann ◽

M. Böer ◽

H.-P. Brandt ◽

J. Pohlenz ◽

...

Keyword(s):

Congo Red ◽

Kidney Diseases ◽

Amyloid Deposition ◽

Panthera Tigris ◽

Aa Amyloidosis ◽

Familial Predisposition ◽

Amyloid A ◽

Panthera Tigris Altaica ◽

Amyloid Deposits ◽

Congo Red Staining

Generalized amyloidosis with predominant renal medullary amyloid deposition was found in four closely related Siberian tigers ( Panthera tigris altaica) suffering from end stage kidney diseases. Only minimal to mild amounts of amyloid were deposited in various organs outside the kidneys with individually variable organ involvement. The Congo red staining affinity of amyloid deposits was sensitive to potassium permanganate oxidation. The deposits were further characterized as being of the amyloid-A (AA) type by immunohistochemistry using the mouse monoclonal antibody mc4 directed against a conserved region of the human AA-protein. A combination of immunohistochemistry and Congo red staining was much more sensitive for the diagnosis of amyloid deposits than Congo red staining alone. With this combination, even minimal amyloid deposits were detected that had been missed in the first reading using Congo-red-stained slides alone. Since no common primary cause was identified, the amyloidosis was classified as idiopathic generalized AA-amyloidosis with a potential familial predisposition.

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Linkage of protection against amyloid fibril formation in the mouse to a single, autosomal dominant gene.

Journal of Experimental Medicine ◽

10.1084/jem.181.6.2249 ◽

1995 ◽

Vol 181 (6) ◽

pp. 2249-2252 ◽

Cited By ~ 13

Author(s):

W A Gonnerman ◽

R Elliott-Bryant ◽

I Carreras ◽

J D Sipe ◽

E S Cathcart

Keyword(s):

Standard Error ◽

Amyloid Fibrils ◽

Single Gene ◽

Dominant Gene ◽

Inbred Strains ◽

Aa Amyloidosis ◽

F1 Hybrid ◽

Amyloid A ◽

Amyloid Enhancing Factor ◽

The Mean

Inbred strains of mice provide a model for studies of the pathogenesis of amyloid A (AA) amyloidosis. All susceptible strains of mice described to date codominantly express two serum amyloid A (apoSAA) isoforms, apoSAA1 and apoSAA2, of which only apoSAA2 serves as a precursor for amyloid fibrils. In previous studies, we have shown that the CE/J strain, which produces a single, novel apoSAA isoform, apoSAACE/J, is amyloid resistant. In the present study amyloid-resistant CE/J females were mated with amyloid-susceptible CBA/J males to produce F1 hybrid offspring which were then backcrossed to the parental CBA/J mouse strain. Amyloid susceptibility was determined in 30 backcrossed mice 72 h after injection of murine amyloid enhancing factor and silver nitrate. ApoSAA isoforms in plasma were separated by isoelectric focusing gel electrophoresis and visualized after immunoblotting with anti-AA antiserum. Amyloid A fibrils in spleen homogenates were denatured by formic acid and AA protein was quantified by ELISA using anti-mouse apoSAA antibodies. Values < 5 apoSAA equivalent units were considered negative. 13 mice expressed an apoSAA1 and apoSAA2 doublet characteristic of CBA/J mice, whereas 17 mice, expressed the apoSAACE/J isoform codominantly with apoSAA1 and apoSAA2. The correlation of amyloid resistance to expression of the apoSAACE/J isoform was absolute (17/17 were negative; mean score 2.6 +/- 0.17 [standard error of the mean] apoSAA equivalent units) and the correlation between amyloid susceptibility and the expression of apoSAA2/apoSAA1 was also striking (12/13 were amyloid positive; mean score 47.9 +/- 9.0 [standard error of the mean] apoSAA equivalent units (P < 0.001). This is not significantly different from the 50% segregation of apoSAA phenotypes expected for linkage to a single gene. These results indicate that a single gene governs apoSAACE/J expression and thus confers protection against amyloid deposition even in the presence of apoSAA1 and apoSAA2 isoforms and show for the first time that resistance to AA amyloidosis is a dominant trait governed by a single gene.

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A temporal and ultrastructural relationship between heparan sulfate proteoglycans and AA amyloid in experimental amyloidosis.

Journal of Histochemistry & Cytochemistry ◽

10.1177/39.10.1940305 ◽

1991 ◽

Vol 39 (10) ◽

pp. 1321-1330 ◽

Cited By ~ 69

Author(s):

A D Snow ◽

R Bramson ◽

H Mar ◽

T N Wight ◽

R Kisilevsky

Keyword(s):

Heparan Sulfate ◽

Amyloid Fibrils ◽

Dermatan Sulfate ◽

Polyclonal Antibodies ◽

Amyloid Deposition ◽

Sulfate Proteoglycan ◽

Aa Amyloidosis ◽

Experimental Amyloidosis ◽

Protein Core ◽

Dermatan Sulfate Proteoglycan

Previous histochemical studies have suggested a close temporal relationship between the deposition of highly sulfated glycosaminoglycans (GAGs) and amyloid during experimental AA amyloidosis. In the present investigation, we extended these initial observations by using specific immunocytochemical probes to analyze the temporal and ultrastructural relationship between heparan sulfate proteoglycan (HSPG) accumulation and amyloid deposition in a mouse model of AA amyloidosis. Antibodies against the basement membrane-derived HSPG (either protein core or GAG chains) demonstrated a virtually concurrent deposition of HSPGs and amyloid in specific tissue sites regardless of the organ involved (spleen or liver) or the induction protocol used (amyloid enhancing factor + silver nitrate, or daily azocasein injections). Polyclonal antibodies to AA amyloid protein and amyloid P component also demonstrated co-localization to sites of HSPG deposition in amyloid sites, whereas no positive immunostaining was observed in these locales with a polyclonal antibody to the protein core of a dermatan sulfate proteoglycan (known as "decorin"). Immunogold labeling of HSPGs (either protein core or GAG chains) in amyloidotic mouse spleen or liver revealed specific localization of HSPGs to amyloid fibrils. In the liver, heparan sulfate GAGs were also immunolocalized to the lysosomal compartment of hepatocytes and/or Kupffer cells adjacent to sites of amyloid deposition, suggesting that these cells are involved in HSPG production and/or degradation. The close temporal and ultrastructural relationship between HSPGs and AA amyloid further implies an important role for HSPGs during the initial stages of AA amyloidosis.

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Amyloid deposition in granuloma of tuberculosis patients: A pilot study

10.1101/2021.02.08.21250526 ◽

2021 ◽

Author(s):

Shreya Ghosh ◽

Akansha Garg ◽

Chayanika Kala ◽

Ashwani Kumar Thakur

Keyword(s):

Serum Amyloid A ◽

Amyloid Deposition ◽

Serum Amyloid ◽

Secondary Amyloidosis ◽

Amyloid Formation ◽

Tuberculosis Patients ◽

Amyloid A ◽

Inflammatory Conditions ◽

Amyloid Deposits ◽

Serum Amyloid A Protein

AbstractThe formation of granuloma is one of the characteristic feature of tuberculosis. Besides, rise in the concentration of acute phase response proteins mainly serum amyloid A is the indicator for chronic inflammation associated with tuberculosis. Serum amyloid A drives secondary amyloidosis in tuberculosis and other chronic inflammatory conditions. The linkage between serum amyloid A (SAA) protein and amyloid deposition site is not well understood in tuberculosis and other chronic inflammatory conditions. We hypothesized that granuloma could be a potential site for amyloid deposition because of the presence of serum amyloid A protein and proteases that cleave SAA and trigger amyloid formation. Based on this hypothesis, for the first time we have shown the presence of amyloid deposits in the granuloma of tuberculosis patients using the gold standard, Congo red dye staining.

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Light Microscopic, Immunohistochemical, and Electron Microscopic Features of Amyloid Arthropathy in Chickens

Veterinary Pathology ◽

10.1177/030098589703400402 ◽

1997 ◽

Vol 34 (4) ◽

pp. 271-278 ◽

Cited By ~ 14

Author(s):

N. H. M. T. Peperkamp ◽

W. J. M. Landman ◽

P. C. J. Tooten ◽

A. Ultee ◽

W. F. Voorhout ◽

...

Keyword(s):

Articular Cartilage ◽

Enterococcus Faecalis ◽

Amyloid Fibrils ◽

Superficial Layer ◽

Immunogold Electron Microscopy ◽

Amyloid Formation ◽

Electron Microscopic ◽

Amyloid A ◽

Amyloid Deposits ◽

Amyloid Arthropathy

Amyloid arthropathy has been recently recognized as a spontaneous syndrome in chickens. Predominantly, femorotibial and tarsometatarsal joints were affected, showing (peri) articular orange amyloid deposits. Immunohistochemical evaluation revealed the amyloid to be of the reactive type. Induction of amyloid arthropathy in chickens was carried out using a single intravenous injection of Enterococcus faecalis cultures. In the naturally occurring and the induced cases, amyloid deposits were found in the hypertrophic synovial villi and in the articular cartilage, particularly in the superficial layer and in the nutritional blood vessel walls. Highly sulfated glycosaminoglycans (GAGs) were found in the amyloid deposits. Ultrastructurally, bundles of amyloid fibrils were seen in invaginations of synoviocytes and chondrocytes. Immunogold electron microscopy failed to reveal signs of intracellular amyloid formation. The predilection site for amyloid deposition in the major leg joints of the chickens with reactive amyloid could be explained by the arthritic condition caused by Enterococcus faecalis bacteriaemia. The polyarthritis triggers hepatic acute phase protein synthesis and increases the vascular serum amyloid A (SAA) supply to the joint. Inflammatory and degenerative changes in the articular cartilage and adjoining tissues result in an increase of highly sulphated GAGs, which are considered to enhance deposition of SAA as amyloid.

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Effective Anti-TNF-α Therapy Can Induce Rapid Resolution and Sustained Decrease of Gastroduodenal Mucosal Amyloid Deposits in Reactive Amyloidosis Associated with Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.090101 ◽

2009 ◽

Vol 36 (11) ◽

pp. 2409-2415 ◽

Cited By ~ 41

Author(s):

TAKESHI KURODA ◽

YOKO WADA ◽

DAISUKE KOBAYASHI ◽

SHUICHI MURAKAMI ◽

TAKEHITO SAKAI ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Aa Amyloidosis ◽

Laboratory Findings ◽

Protein Levels ◽

Amyloid A ◽

Biopsy Specimens ◽

Amyloid Deposits ◽

Reactive Amyloidosis ◽

Serum Amyloid A Protein ◽

Before And After

Objective.To examine the effect of anti-tumor necrosis factor-α (anti-TNF) therapy in patients with reactive AA amyloidosis associated with rheumatoid arthritis (RA).Methods.Fourteen patients with reactive AA amyloidosis associated with RA were prospectively evaluated. Four patients were treated with infliximab and 10 with etanercept. The mean period of anti-TNF therapy was 20.1 ± 13.8 months. Laboratory findings and renal function were examined before and after initiation of anti-TNF therapy. In 9 patients the area of amyloid deposits in serial gastroduodenal mucosal biopsy specimens was examined and image analysis was performed.Results.C-reactive protein and serum amyloid A protein levels were significantly reduced after initiation of anti-TNF therapy. Twenty-four hour creatinine clearance improved in 4 patients, did not change in 5, and deteriorated in 3. Twenty-four hour urinary protein excretion was significantly decreased in 3 patients, not exacerbated in 6, and increased in 3 after initiation of anti-TNF therapy. The biopsy specimens from the 9 patients who underwent serial gastroduodenal biopsies showed significant decreases in the area of amyloid deposits, from 8.8% ± 6.4% to 1.6% ± 0.6% (p = 0.003) after initiation of anti-TNF therapy. Four patients showed a sustained decrease in the areas of amyloid deposits in their third biopsy specimens, and amyloid deposits were not detectable in 2.Conclusion.Our results indicate a striking effect of anti-TNF therapy for rapid removal and sustained disappearance of amyloid deposits in gastric mucosal tissue with amelioration of renal functions in patients with reactive amyloidosis due to RA.

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