Amyloidosis defines a heterogeneous group of diseases of differents origin characterized by proteinaceous tissue deposits that show green birefringence in polarized light after Congo red staining.
This is an insoluble protein, protease resistant and β-sheet folding.
Type of amyloidosis:
1. Primary: it is not proceed by any particular pathology
2. Secondary: it is proceed by weaken Chronic inflammations
3. Associated to a multiple myeloma: on 15% of patients by this pathology affected.
The β-sheet folding explained by two differents hypothesis: mutation of the amino acidic sequence or wrong proteolytic cleavages.
Amyloid is made by:
- 90% of protein fibrils (characteristic of each disease)
- the remaining part is constituted by
- amyloid P component (glycoproteic)
- solforate GAGs.
There are many type of amyloidosis and this is due to the different proteins (at least 23) that may change their structure.
ATTR, Transthyretin, Aβ2M, AA
The amyloidosis diagnosis required the amyloid deposit identification, by specific staining, of a tissue sample. Normally is used the FNA of periumbilical fat.
Amyloid Light-chain (AL) amyloidosis, primary systemic amyloidosis
Immunoglobulin Light (Heavy)-Chain Deposition Disease: From Molecular Medicine to Pathophysiology-Driven Therapy, 2006
- Light-, light- and heavy-, and heavy-chain deposition diseases belong to a family of diseases that include light-chain (AL)-amyloid, nonamyloid fibrillary and immunotactoid glomerulonephritis, and cryoglobulinemic glomerulonephritis, in which monoclonal Ig or their subunits become deposited in kidney. In clinical and pathologic terms, light-, light- and heavy-, and heavy-chain deposition diseases essentially are similar and are characterized by prominent renal involvement with severe renal failure; extrarenal manifestations; diabetes-like nodular glomerulosclerosis; marked thickening of tubular basement membranes; and monotypic deposits of light chain, mostly κ, and/or heavy chain that feature a nonorganized granular, electron-dense appearance by electron microscopy. The most common cause is myeloma. Recent progress has been made in the understanding of the molecular pathomechanisms of Ig-chain deposition and extracellular matrix accumulation, which opens up new therapeutic avenues in addition to eradication of the Ig-secreting plasma cell clone. Because these diseases represent a model of glomerular and interstitial fibrosis that is induced by a single molecule species, a better understanding of their pathomechanisms may help to unravel the pathophysiology of kidney fibrosis and renal disease progression.
The goals are:
1) The reduction of the amyloid precursor production;
2) The Inhibition of the amyloid fibrils synthesis and the extracellular deposition;
3) The enhanced mobilization of the existing amyloid deposition.
Created by: Laura SOLFIETTI, Letizia GRANIERI, Alessandra RUSSO