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 Overview of systemic and localized amyloidosis

2013 ◽  
Vol 4 (4) ◽  
pp. 231-247 ◽  
Author(s):  
Saulius Girnius
Keyword(s):  
Protein Misfolding ◽  
Clinical Manifestations ◽  
Organ Damage ◽  
Precursor Protein ◽  
Al Amyloidosis ◽  
Folding Intermediates ◽  
Amyloid A ◽  
Localized Amyloidosis ◽  
Amyloid Deposits ◽  
Cell Transplants

Amyloidosis is a family of protein misfolding disorders, in which insoluble fibrillar proteins deposit extracellularly and cause end organ damage. Depending on the precursor protein, clinical manifestations in amyloidosis vary significantly. In systemic amyloidosis, the heart, kidneys, and nerves are most commonly affected, resulting in congestive heart failure, arrhythmia, nephrotic syndrome, renal failure, and peripheral and autonomic neuropathies. In localized amyloidosis, amyloid deposits at the site of production, so only one organ is disrupted. Once amyloidosis is confirmed histologically, the precursor subtype must be identified using immunohistochemistry, immunofixation, electron microscopy, or laser microdissection and mass spectrometry. Treatment should not be initiated prior to the identification of the type of amyloidosis. Currently, treatment focuses on the suppression of the precursor protein: in AL amyloidosis, chemotherapy or autologous stem cell transplants suppress production of immunoglobulin light chains; in AA amyloidosis, anti-microbial and anti-inflammatory agents suppress amyloid A production; and in AF amyloidosis, a liver transplantation removes the source of mutant transthyretin protein production. Newer drugs are being developed to target amyloidosis at an epigenetic level or stabilize folding intermediates, but there are currently in development.

scholarly journals Amyloid deposition in granuloma of tuberculosis patients: A pilot study

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.

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

1997 ◽  
Vol 34 (4) ◽  
pp. 271-278 ◽  
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.

scholarly journals Should the Reporting of Bone Marrow Positivity for Amyloid Be Revised?: A Critical Assessment Based on 66 Biopsies From a Single Institution

2020 ◽  
Vol 144 (8) ◽  
pp. 967-973 ◽  
Author(s):  
Sara Javidiparsijani ◽  
Maria M. Picken
Keyword(s):  
Bone Marrow ◽  
Spatial Distribution ◽  
Plasma Cells ◽  
Treatment Options ◽  
Clinical Information ◽  
Al Amyloidosis ◽  
Significant Heterogeneity ◽  
Amyloid A ◽  
Amyloid Deposits ◽  
Amyloid Light Chain

Context.— Amyloidoses are rare but heterogeneous disorders for which diagnosis is contingent upon the detection of deposits by Congo red stain and amyloid protein typing determines the treatment options. Objective.— To address the reporting of bone marrow (BM) involvement by amyloid in relation to the spatial distribution of deposits and to explore whether the location of deposits may have clinical relevance. Design.— We examined 66 BM biopsies positive for amyloid with regard to the location and type of amyloid, the percentage and clonality of plasma cells, other organ involvement, and relevant clinical information. Results.— In 21 cases, amyloid deposits involved BM stroma, whereas 45 cases were nonstromal. All cases of stromal involvement were typed as amyloid light chain (AL) amyloidosis (or presumed AL), whereas nonstromal involvement was associated with at least 3 types of amyloidosis: AL, amyloid transthyretin (ATTR), and amyloid A (AA). The initial diagnosis of amyloidosis was made in a BM specimen in 21 of 66 cases (31.8%). Plasma cells ranged from 1% to 80% (mean, 13.4%; median, 8%; <10% in 44 of 66 specimens [66.6%]) and were monoclonal in 58 of 66 cases (87.8%), and in 54 of 66 cases (81.8%) amyloid deposits were documented in at least one other organ. Conclusions.— This study demonstrates that there is significant heterogeneity in the spatial distribution of amyloid in BM biopsy specimens with medullary, extramedullary, purely vascular, or combined involvement. Whereas stromal deposits were associated exclusively with AL, nonstromal and purely vascular deposits were seen in at least 3 types of systemic amyloidosis (AL, AA, and ATTR). We discuss the reporting of BM biopsy tissue positivity for amyloid deposits.

scholarly journals Immunoglobulin light chain amyloidosis

2021 ◽  
Author(s):  
Hermine Agis ◽  
Maria T. Krauth
Keyword(s):  
Light Chain ◽  
Systemic Disease ◽  
Correct Diagnosis ◽  
Organ Damage ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Multiprofessional Team ◽  
Assessment And Treatment ◽  
Life Threatening ◽  
Immunoglobulin Light Chain Amyloidosis

SummaryImmunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed life-threatening systemic disease, primarily caused by insoluble depositions of misfolded monoclonal light chains. The monoclonal light chain paraprotein originates from a small clonal B‑cell or a clonal plasma cell population. If left undetected the paraprotein can induce a number of complications based on organ damage. The most dangerous and life-threatening organ dysfunction emerges from cardiac involvement. Thus, patients overall survival depends on early detection. Establishing the correct diagnosis and clear characterization of the amyloid-forming protein, staging, risk assessment and treatment are crucial and depend on a highly experienced interdisciplinary, multiprofessional team.

scholarly journals Supportive Care in AL Amyloidosis

2020 ◽  
Vol 143 (4) ◽  
pp. 335-342 ◽  
Author(s):  
M. Teresa Cibeira ◽  
José T. Ortiz-Pérez ◽  
Luis F. Quintana ◽  
Carlos Fernádez de Larrea ◽  
Natalia Tovar ◽  
...  
Keyword(s):  
Supportive Care ◽  
Light Chain ◽  
Amyloid Fibrils ◽  
Cell Clone ◽  
Systemic Disease ◽  
Complex Interventions ◽  
Al Amyloidosis ◽  
Salt Restriction ◽  
Organ Response

Immunoglobulin light-chain (AL) amyloidosis is a systemic disease characterized by the production and deposition of light chain-derived amyloid fibrils in different organs. Prompt treatment directed to the underlying plasma cell clone is crucial in order to achieve a rapid, deep and durable hematologic response. The decrease in the production of the amyloidogenic light chains is a required condition to obtain the organ response, which is commonly delayed. Meanwhile, supportive treatment is aimed to maintain quality of life of these patients and preserve their involved organs’ function. From simple measures, such as salt restriction or compressive stockings, to very complex interventions, such as heart transplantation in very selected patients with isolated severe cardiac involvement, this supportive care is essential and has to be necessarily included in the multidisciplinary management of this disease.

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.

The Effect of Sedation, Oral Examination, and Odontoplasty on Systemic Inflammation as Measured by Serum Amyloid A in the Adult Performance Horse

2019 ◽  
Vol 36 (3) ◽  
pp. 198-201
Author(s):  
Sheri S. W. Birmingham ◽  
Rocky M. Mason
Keyword(s):  
Systemic Inflammation ◽  
Serum Amyloid A ◽  
Acute Phase Proteins ◽  
Systemic Disease ◽  
Oral Examination ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Adult Performance ◽  
Normal Limits ◽  
Time Periods

Serum amyloid A (SAA) is one of the major acute phase proteins in horses. It serves as a marker for systemic inflammation and infection, as the concentration can increase 100- to even 1000-fold during systemic disease processes. The objective of this study was to evaluate the effect of sedation, oral examination, and odontoplasty on systemic inflammation as measured by SAA in the adult performance horse. This study included 32 clinically healthy adult performance horses. Blood samples were collected immediately prior to sedation, oral examination, and odontoplasty and 48 and 72 hours afterward. Serum amyloid A levels were measured directly after venipuncture using a commercially available stall-side lateral flow immunoassay test developed and validated for equine SAA levels. Serum amyloid A values were within normal limits for each of the time periods and there were no significant differences in SAA values between the time periods. The results of this study suggest that sedation, oral examination, and odontoplasty have no systemic inflammatory effects as measured by SAA.

Testicular Involvement is a Hallmark of Apo A-I Leu75Pro Mutation Amyloidosis

2020 ◽  
Vol 105 (12) ◽  
pp. e4758-e4766
Author(s):  
Andrea Delbarba ◽  
Paolo Facondo ◽  
Simona Fisogni ◽  
Claudia Izzi ◽  
Filippo Maffezzoni ◽  
...  
Keyword(s):  
Follicle Stimulating Hormone ◽  
Organ Damage ◽  
University Hospital ◽  
Reproductive Hormone ◽  
Testicular Dysfunction ◽  
Amyloid Deposits ◽  
Scrotal Ultrasound ◽  
Almost All ◽  
The University ◽  
Male Subjects

Abstract Context Apo A-I Leu75Pro is a rare hereditary form of amyloidosis that mainly involves the kidney, the liver, and the testis. Objective To define the characteristics of organ damage and testis impairment in the largest cohort collected to date of men with Apo A-I Leu75Pro amyloidosis. Design, Setting, and Patients Retrospective study from a prospectively collected database of 129 male subjects >18 years with Apo A-I Leu75Pro amyloidosis from a reference center at the University Hospital of Brescia, Italy. Main outcome measures We evaluated liver and renal function, scrotal ultrasound, reproductive hormone levels, testis biopsy, hypogonadal symptoms, and fertility. Results Progressive involvement of testis, kidney, and liver was observed in 96/129 (74.4%) cases. Testis impairment was found in 88/129 patients (68.2%), liver in 59 (45.7%) and renal in 50 (38.8%). Testis damage was often the first manifestation of the disease and the only dysfunction in 30% of younger patients (<38 years). Testicular involvement was characterized mainly by primary (73/88 patients, 83.0%) and subclinical (8/88, 9.1%) hypogonadism. Almost all (85/88, 96.6%) also had high follicle-stimulating hormone, suggesting a primary global damage of endocrine and spermatogenic functions, and 30% of them did not conceive. Macroorchidism was found in 53/88 (60.2%) patients, especially in men <54 years (30/33, 90.9%). Apo A-I amyloid deposits were found in Sertoli cells, germinal epithelium, and vessel walls. Conclusion In men with Apo A-I Leu75Pro amyloidosis, testicular involvement is the hallmark of the disease, characterized by global primary testicular dysfunction and macroorchidism due to amyloid deposits.

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