Amyloidosis
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Amyloidosis Microchapters |
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Diagnosis |
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Amyloidosis On the Web |
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American Roentgen Ray Society Images of Amyloidosis |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]
Overview
In 1639, Nicolaus Fontanus autopsied a young man who had ascitis, jaundice, liver abscess and splenomegaly and his report has been the first description of amyloidosis. and in 1959, Cohen and Calkins assessed an ultra-thin sections of amyloidotic tissues by electron microscopic examination. Amyloidosis may be classified based on precursor of amyloidogenic protein into different subtypes, include AL amyloidosis (Light chains of immunoglobulines), AA amyloidosis (Serum amyloid A protein), AF amyloidosis (Mutant transthyretin, A1-apolipoprotein, gelsolin, fibrinogen, etc.), ATTRwt amyloidosis (Wild-type transthyretin), and AH amyloidosis (ß2-microglobulin). Amyloidosis also may classified by their extension of organ involvement as systemic amyloidosis (primary amyloidosis, secondary amyloidosis, hereditary amyloidosis) and Organ-specific amyloidosis (cardiac amyloidosis, hepatic amyloidosis, renal amyloidosis, etc.). Amyloid is an abnormal insoluble extracellular protein that deposits in the different tissues and causes organic dysfunction. These abnormal amyloids derived from misfolding and aggregation of normally soluble proteins. In systemic amyloidosis, amyloid gradually accumulate and amyloid deposition is widespread in the viscera, blood vessel walls, and in the different connective tissues. In organ-specific amyloidoses, amyloid deposition occurs only in the origin organ or tissue of precursor protein. In microscopy pathology of amyloidosis, amyloid is detectable as typical green birefringence under polarized light after Congo red staining, linear non-branching fibrils, distinct X-ray diffraction pattern consistent with Pauling's model of a cross-beta fibril.
Historical Perspective
- In 1639, Nicolaus Fontanus autopsied a young man who had ascitis, jaundice, liver abscess and splenomegaly and his report has been the first description of amyloidosis.[1]
- In 1854, Rudolph Virchow introduced the term of amyloid as an macroscopic abnormality in some tissues.[2]
- In 1867, Weber reported the first case of amyloidosis associated with multiple myeloma.[1]
- In 1922, Bennhold introduced Congo red staining of amyloid that remains the gold standard for diagnosis.[3]
- In 1959, Cohen and Calkins used ultra-thin sections of amyloidotic tissues and assessed by electron microscopic examination, explained the presence of non-branching fibrils with indeterminate length and variable width.[2][1]
Classification
Amyloidosis may be classified based on precursor of amyloidogenic protein into different subtypes, include:[4][5]
| Type | Amyloidogenic protein/ fibril | Clinical syndrome |
|---|---|---|
| AL (primary amyloidosis) | Light chains of immunoglobulines (most common type) | Monoclonal gammopathy |
| AA (secondary amyloidosis) | Serum amyloid A protein | Chronic inflammatory diseases |
| AF | Mutant transthyretin, A1-apolipoprotein, gelsolin, fibrinogen, etc. | Familial polyneuropathy/cardiomyopathy/nephropathy |
| ATTRwt | Wild-type transthyretin | Senile restrictive cardiomyopathy _ Transthyretin-related amyloidosis wild-type |
| AH | ß2-microglobulin | Long-term hemodialysis |
Amyloidosis also may classified by their extension of organ involvement as below:[6][7]
| Classification | subtypes | Causes | Important clinical findings |
|---|---|---|---|
| Systemic amyloidosis | Primary amyloidosis (AL) |
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| Secondary amyloidosis (AA) |
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| Hereditary amyloidosis | |||
| Organ-specific amyloidosis | Renal amyloidosis |
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| Cardiac amyloidosis | |||
| Hepatic amyloidosis |
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| Amyloid neuropathy | |||
| Gastrointestinal amyloidosis |
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Pathophysiology
- Amyloid is an abnormal insoluble extracellular protein that deposits in the different tissues and causes organic dysfunction and a wide variety of clinical syndromes.[8][9]
- These abnormal amyloids derived from misfolding and aggregation of normally soluble proteins.[10]
- Amyloid deposition can disrupt tissue structure of involved organ and consequently leads to organ failure.[11]
Systemic Amyloidosis
- In systemic amyloidosis, amyloid gradually accumulate and amyloid deposition is widespread in the viscera, blood vessel walls, and in the different connective tissues.[9][10]
Primary Amyloidosis (AL)
- Primary (AL) amyloidosis) is the most common type of amyloidosis. It results from aggregation and deposition of monoclonal immunoglobulin (Ig) light chains that usually produced by plasma cell clones.
- Change in the secondary structure or tertiary structure of a monoclonal light chain results in abnormal folding of the light chain that abnormally form amyloid fibrils.[12]
- This type of amyloidosis most frequently involve the kidney (usually proteinuria with the nephrotic syndrome) and the heart.[13]
- In primary (AL) amyloidosis survival rate depends on:[14]
- Type of organ involvement (amyloid heart disease is the main prognostic factor)
- The severity of different organs involvement
- Haematological response to treatment
- The median survival of patients with AL amyloidosis is aproximately 3.8 years.[15]
For more information about primary amyloidosis click here.
Secondary Amyloidosis (AA)
- Secondary amyloidosis is associated with chronic inflammation (such as tuberculosis or rheumatoid arthritis).[13]
- Secondary or reactive amyloidosis (AA) is approximately 45% of all systemic amyloidosis.[16]
- Pathogenesis of secondary amyloidosis is multifactorial that include:
- Primary structure of the precursor protein
- Acute phase response
- Nonfibril proteins (amyloid P component, apo E, GAGs, proteoglycans and basement membrane proteins)
- Receptors
- Lipid metabolism
- Proteases
For more information about secondary amyloidosis click here.
Hereditary Amyloidosis
- Hereditary (or familial) amyloidosis are autosomal dominant diseases that inherited variant proteins cause the production and deposition of amyloid fibrils.[13]
- Hereditary amyloidosis are due to amyloidogenic mutations and subsequently deposition of amyloids, include:[17]
Organ-specific Amyloidosis
- In this type of amyloidoses, amyloid deposition occurs only in the origin organ or tissue of precursor protein.[18]
- Some neurodegenerative disorders such as Parkinson's disease, Alzheimer, and Huntington's disease may occur in localised amyloidosis.
- Localised amyloidoses can accure due to deposition of intracellular and/or extracellular amyloid.
- Huntington's disease: intracellular protein deposition
- Parkinson's disease: intracellular protein deposition
- Alzheimer's disease: intracellular (Tau protein fibrils) and extracellular (amyloid β fibrils) deposition
Microscopic Pathology
In microscopy pathology of amyloidosis, amyloid is detectable as:[16][13]
- Typical green birefringence under polarized light after Congo red staining (appears in red under normal light)
- Linear non-branching fibrils (indefinite length with an approximately same diameter)
- Distinct X-ray diffraction pattern consistent with Pauling's model of a cross-beta fibril
Case Studies
- ↑ 1.0 1.1 1.2 Kyle RA (June 2011). "Amyloidosis: a brief history". Amyloid. 18 Suppl 1: 6–7. doi:10.3109/13506129.2011.574354001. PMID 21838413.
- ↑ 2.0 2.1 Sipe JD, Cohen AS (June 2000). "Review: history of the amyloid fibril". J. Struct. Biol. 130 (2–3): 88–98. doi:10.1006/jsbi.2000.4221. PMID 10940217.
- ↑ Khan MF, Falk RH (November 2001). "Amyloidosis". Postgrad Med J. 77 (913): 686–93. PMC 1742163. PMID 11677276.
- ↑ Real de Asúa D, Costa R, Galván JM, Filigheddu MT, Trujillo D, Cadiñanos J (2014). "Systemic AA amyloidosis: epidemiology, diagnosis, and management". Clin Epidemiol. 6: 369–77. doi:10.2147/CLEP.S39981. PMC 4218891. PMID 25378951.
- ↑ Misumi Y, Ando Y (July 2014). "[Classification of amyloidosis]". Brain Nerve (in Japanese). 66 (7): 731–7. PMID 24998818.
- ↑ Bilginer Y, Akpolat T, Ozen S (August 2011). "Renal amyloidosis in children". Pediatr. Nephrol. 26 (8): 1215–27. doi:10.1007/s00467-011-1797-x. PMC 3119800. PMID 21360109.
- ↑ Khoor A, Colby TV (February 2017). "Amyloidosis of the Lung". Arch. Pathol. Lab. Med. 141 (2): 247–254. doi:10.5858/arpa.2016-0102-RA. PMID 28134587.
- ↑ Gillmore JD, Hawkins PN (October 2013). "Pathophysiology and treatment of systemic amyloidosis". Nat Rev Nephrol. 9 (10): 574–86. doi:10.1038/nrneph.2013.171. PMID 23979488.
- ↑ 9.0 9.1 Baker KR, Rice L (2012). "The amyloidoses: clinical features, diagnosis and treatment". Methodist Debakey Cardiovasc J. 8 (3): 3–7. PMC 3487569. PMID 23227278.
- ↑ 10.0 10.1 Pepys MB (2006). "Amyloidosis". Annu. Rev. Med. 57: 223–41. doi:10.1146/annurev.med.57.121304.131243. PMID 16409147.
- ↑ Jerzykowska S, Cymerys M, Gil LA, Balcerzak A, Pupek-Musialik D, Komarnicki MA (2014). "Primary systemic amyloidosis as a real diagnostic challenge - case study". Cent Eur J Immunol. 39 (1): 61–6. doi:10.5114/ceji.2014.42126. PMC 4439975. PMID 26155101.
- ↑ Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B, Quellard N, Lacombe C, Goujon JM, Lavergne D, Abraham J, Touchard G, Fermand JP, Jaccard A (August 2012). "Al amyloidosis". Orphanet J Rare Dis. 7: 54. doi:10.1186/1750-1172-7-54. PMC 3495844. PMID 22909024.
- ↑ 13.0 13.1 13.2 13.3 Khan MF, Falk RH (November 2001). "Amyloidosis". Postgrad Med J. 77 (913): 686–93. PMC 1742163. PMID 11677276.
- ↑ Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B, Quellard N, Lacombe C, Goujon JM, Lavergne D, Abraham J, Touchard G, Fermand JP, Jaccard A (August 2012). "Al amyloidosis". Orphanet J Rare Dis. 7: 54. doi:10.1186/1750-1172-7-54. PMC 3495844. PMID 22909024.
- ↑ Merlini G, Seldin DC, Gertz MA (May 2011). "Amyloidosis: pathogenesis and new therapeutic options". J. Clin. Oncol. 29 (14): 1924–33. doi:10.1200/JCO.2010.32.2271. PMC 3138545. PMID 21483018.
- ↑ 16.0 16.1 Röcken C, Shakespeare A (February 2002). "Pathology, diagnosis and pathogenesis of AA amyloidosis". Virchows Arch. 440 (2): 111–122. doi:10.1007/s00428-001-0582-9. PMID 11964039.
- ↑ Mahmood S, Palladini G, Sanchorawala V, Wechalekar A (February 2014). "Update on treatment of light chain amyloidosis". Haematologica. 99 (2): 209–21. doi:10.3324/haematol.2013.087619. PMC 3912950. PMID 24497558.
- ↑ Blancas-Mejía LM, Ramirez-Alvarado M (2013). "Systemic amyloidoses". Annu. Rev. Biochem. 82: 745–74. doi:10.1146/annurev-biochem-072611-130030. PMC 4044913. PMID 23451869.