scholarly journals High-sensitivity diagnosis of AA amyloidosis using Congo red and immunohistochemistry detects missed amyloid deposits.

1995 ◽  
Vol 43 (9) ◽  
pp. 863-869 ◽  
Author(s):  
R P Linke ◽  
H V Gärtner ◽  
H Michels
Keyword(s):  
Congo Red ◽  
High Sensitivity ◽  
Organ Damage ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Biopsy Specimens ◽  
Pediatric Diseases ◽  
Amyloid Deposits ◽  
Renal Biopsies ◽  
Rectal Biopsies

Biopsy diagnosis of early amyloid-A (AA) amyloidosis has often been difficult. Examination of 57 consecutive biopsy specimens from 42 patients with inflammatory pediatric diseases permitted comparison of the precision of biopsy amyloid diagnosis in six different laboratories (labs), which applied the following methods: Congo red alone (four unspecialized labs combined as Lab 1), Congo red and electron microscopy (Lab 2), or Congo red and immunohistochemistry using monoclonal antibodies (Lab 3). Lab 3 reexamined the diagnoses made by Lab 1 and Lab 2. Of the 42 patients, 17 patients with 32 biopsies were selected for this study based on the presence of amyloid in at least one biopsy. Whereas massive or no amyloid was concordantly recognized by all labs in 18 biopsies from nine patients, discordance was demonstrated in 14 biopsies from eight patients. Comparison of Labs 1-3 revealed amyloid in 12 rectal and 18 renal biopsies evaluated by Lab 3, whereas Lab 2 missed amyloid in two of 18 renal biopsies and Lab 1 missed amyloid in 11 of 12 rectal biopsies. Most amyloid was missed when only minute amounts of amyloid were present. Had our technique (Lab 3) been available at the time of biopsy, amyloid could have been diagnosed years earlier, thereby sparing the patient further biopsies and allowing initiation of earlier treatment before organ damage could occur.

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

2009 ◽  
Vol 36 (11) ◽  
pp. 2409-2415 ◽  
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.

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

1998 ◽  
Vol 35 (1) ◽  
pp. 70-74 ◽  
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.

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

2016 ◽  
Vol 54 (1) ◽  
pp. 99-110 ◽  
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.

The patient with amyloidosis

2015 ◽  
Author(s):  
Helen J. Lachmann ◽  
Giampaolo Merlini
Keyword(s):  
Incidental Finding ◽  
Systemic Disease ◽  
Acute Phase Reactant ◽  
Organ Damage ◽  
Al Amyloidosis ◽  
Amyloid Formation ◽  
Heavy Proteinuria ◽  
Amyloid A ◽  
Amyloid Deposits

Amyloidosis is a disorder of protein folding in which normally soluble plasma proteins are deposited in the extracellular space in an abnormal insoluble fibrillar form. The process of amyloid formation and deposition causes cytotoxicity and progressive organ dysfunction. Amyloid is remarkably diverse and can be hereditary or acquired, localized or systemic, and lethal or merely an incidental finding. The most important numerically are AL amyloidosis, in which the fibrils are composed of monoclonal immunoglobulin light chains, and AA amyloidosis, in which the acute phase reactant Serum Amyloid A component forms the fibrils.The kidney is involved in 75% of patients with systemic amyloidosis. Heavy proteinuria or nephrotic syndrome is characteristic of most amyloid variants.Without treatment, systemic disease is usually fatal but measures that reduce the supply of amyloid fibril precursor proteins can result in regression of amyloid deposits, prevention of organ failure, and improved quality of life and survival. Early diagnosis, before irreversible organ damage has occurred, is the key to effective treatment. Recent advances in diagnosis and therapy have much improved the outlook of patients with AL amyloidosis, but agents with broader promise are under investigation.

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

2017 ◽  
Vol 54 (6) ◽  
pp. 912-921 ◽  
Author(s):  
Yumi Nakayama ◽  
Junichi Kamiie ◽  
Gen Watanabe ◽  
Kazuhiko Suzuki ◽  
Tomoaki Murakami
Keyword(s):  
Japanese Quail ◽  
Intestinal Tract ◽  
Amyloid Fibrils ◽  
Amyloid Deposition ◽  
Coturnix Japonica ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Amyloid Deposits ◽  
Amyloid Enhancing Factor ◽  
Apparently Healthy

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.

scholarly journals Colocalization of Apolipoprotein AI in Various Kinds of Systemic Amyloidosis

2005 ◽  
Vol 53 (2) ◽  
pp. 237-242 ◽  
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.

scholarly journals Generalized AA-Amyloidosis in a Bat (Pipistrellus pipistrellus)

1996 ◽  
Vol 33 (4) ◽  
pp. 428-430 ◽  
Author(s):  
A. D. Gruber ◽  
R. P. Linke
Keyword(s):  
Monoclonal Antibodies ◽  
Salivary Glands ◽  
Potassium Permanganate ◽  
Congo Red ◽  
Chronic Wound ◽  
Aa Amyloidosis ◽  
Female Adult ◽  
Pipistrellus Pipistrellus ◽  
Amyloid Deposits ◽  
Congo Red Staining

Generalized amyloidosis was found to be the cause of death in a female adult insectivorous pipistrelle bat ( Pipistrellus pipistrellus) after chronic wound inflammation. Large amounts of amyloid were detected in liver, spleen, kidneys, stomach, intestine, lymphatic tissues, and endocrine and salivary glands. Congo red staining and green birefringence identified amyloid; the Congo red staining was sensitive to potassium permanganate oxidation. The amyloid was further classified immunohistochemically. The deposits reacted with two anti-human-AA-amyloid monoclonal antibodies in a peroxidase-antiperoxidase reaction, whereas no reaction was found with antibodies specific for other types of amyloid. Thus, the bat amyloid deposits were identified as generalized reactive AA-amyloidosis.

Typing of Amyloidosis in Renal Biopsies: Diagnostic Pitfalls

2007 ◽  
Vol 131 (6) ◽  
pp. 917-922 ◽  
Author(s):  
Anjali A. Satoskar ◽  
Kelly Burdge ◽  
Daniel J. Cowden ◽  
Gyongyi M. Nadasdy ◽  
Lee A. Hebert ◽  
...  
Keyword(s):  
Light Chain ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Immunofluorescence Staining ◽  
Moderate Intensity ◽  
Light Chains ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Renal Biopsies ◽  
Diagnostic Pitfalls

Abstract Context.—Amyloidosis represents a group of diseases with extracellular deposition of congophilic fibrils of similar morphology but differing chemical composition. The types commonly involving the kidney are AL (light chain amyloid) and AA (serum amyloid A). Familial amyloidosis can also affect the kidney, but we have not encountered such a case during the study period. Distinguishing between the AL and AA forms of amyloid is clinically important because of the different treatments and outcomes. The classification of amyloidosis is made by immunostaining with antibodies to κ and λ immunoglobulin light chains and for serum amyloid A protein. Objective.—To draw attention to the nonspecific immunofluorescence staining patterns in renal biopsies with amyloidosis, causing potential diagnostic pitfalls. Design.—Renal biopsies from 15 patients, including 13 cases of AL and 2 cases of AA amyloidosis, were studied. Immunofluorescence staining with routine antibody panel and immunoperoxidase staining for amyloid A were performed. Results.—Of the 13 cases of AL amyloidosis, 2 cases showed little difference in staining intensity between κ and λ light chains (2+ and 3+, respectively) and 4 cases showed only moderate intensity (2+) of the predominant light chain. The 2 cases diagnosed as AA amyloidosis also exhibited staining for light chains. One case had strong (3+) signal for κ and moderate (2+) for λ light chain, while the other showed weaker staining. Conclusions.—Immunofluorescence staining for immunoglobin light chains on renal biopsy, as the first step to differentiate between AL and AA amyloidosis, may sometimes be inconclusive or even misleading. Applying amyloid A immunostain on a routine basis and detailed clinical history are essential to avoid misclassification.

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

2016 ◽  
Vol 54 (1) ◽  
pp. 111-118 ◽  
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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