2° anno Scuola di specializzazione in PATOLOGIA CLINICA
Corso di Biochimica Sistematica
Relazione di: Laura SOLFIETTI, Letizia GRANIERI, Alessandra RUSSO
Amyloidosis
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 b-sheet folding.
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 b-sheet folding is explained by two differents hypothesis: mutation of the amino acidic sequence or wrong proteolytic cleavages.
Any amyloidosis is made by: 90% of protein fibrils (characteristic of each disease), the remaining part is constituted by amyloid P component (glycoproteic) and solforate GAGs.
PATOGENESYS AND CLASSIFICATION
There are many type of amyloidosis and this is due to the different proteins (at least 23) that may change their structure.
|
Protein Amyloid |
Precursor |
Systemic (S) o Localized (L) |
Syndrome o involved tissue |
Involved organ |
|
AL |
Light chain of Ig |
S, L |
Primary, Myeloma associated |
kidney, heart, liver, SNP, SNA |
|
S |
Senile systemic |
PNS, heart, ANS |
||
|
β2- microglobulin |
S |
Hemodialysis-associated |
articulation, bones |
|
|
(Apo)serum AA |
S |
Secondary, reactive |
liver, kidney, ANS |
|
|
AApoA-I |
Apolipoprotein AI |
S |
Familial |
liver, kidney, heart, testicle |
|
AApoA-II |
Apolipoprotein AII |
S |
Familial |
kidney, heart |
|
AGel |
Gelsolin |
S |
Familial |
PNS, cranic nerves, skin |
|
ALys |
Lysozyme |
S |
Familial |
kidney, liver and spleen |
|
AFib |
Fibrinogen a-chain |
S |
Familial |
Kidney |
|
ACys |
Cystatin C |
S |
Familial |
CNS |
|
ABri |
ABriPP |
L |
Familial dementia |
CNS |
|
ADan |
ADanPP |
L |
Familial dementia |
CNS |
|
Aβ |
Ab protein precursor |
L |
CNS |
|
|
AprP |
Prion protein |
L |
Spongioform encephalopathies |
CNS |
|
ACal |
(Pro)calcitonin |
L |
C-cell thyroid tumors |
Thyroid |
|
AIAPP |
Islet amyloid polypeptide |
L |
Islets of Langerhans Insulinomas |
Pancreas |
|
AANF |
Atrial natriuretic factor |
L |
Cardiac atria |
Heart |
|
Apro |
Prolactin |
L |
Aging pituitary Prolactinomas |
Pituitary |
|
AIns |
Insulin |
L |
Iatrogenic |
Injection seat |
|
Amed |
Lactadherin |
L |
Senile aortic, media |
aortic |
|
Aker |
Kerato-epithelin |
L |
Familial |
Cornea |
|
A(tbn) |
tbn |
L |
Odontogenic tumors |
|
|
ALac |
Lactoferrin |
L |
Cornea |
Cornea |
|
SNA, sistema nervoso autonomo; SNP, sistema nervoso periferico; SNC, sistema nervoso centrale. |
||||
DIAGNOSIS
The amyloidosis diagnosis required the amyloid deposit identification, by specific staining, of a tissue sample. Normally is used the FNA of periumbilical fat.
THERAPY
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.