Immunology

Dr.Ziyad 7 -11-2018

Amyloidosis
Amyloid is an insoluble proteinaceous material that are abnormally deposited in tissue interstitium with consequent impairment of function.
Chemical composition: 95% of amyloid material consists of fibril protein (Hence the new name β-fibrillosis) and 5% is the P-component which is a glycoprotein similar to C-reactive protein. Chemically, more than 20 distinct types are identified, three of them are the most common and most important:
AL (amyloid light chain) is derived from the plasma cells and contains Ig light chain and deposits in the tissues of patients with plasma cell dyscrasias like multiple myeloma.
AA (amyloid associated) which is derived from serum amyloid associated protein (SAA) that is synthesized by the liver in chronic inflammations.
Aβ amyloid is found in the cerebral lesion of Alzheimer disease.
Several other biochemically distinct proteins have been found in amyloid deposits in a variety of clinical settings:
--- Transthyretin (TTR) is a normal serum protein that bind and transports thyroxine and retinol. A mutant form of transthyretin is deposited in a group of genetic disorder called familial amyloid polyneuropathy. Normal form of transthyretin is deposited in the heart of aged individuals ( senile systemic amyloidosis).
---- β2-microglobulin (Aβ2m) has been identified in amyloidosis that complicates the course of long term hemodialysis.
---- Amyloid deposits derived from diverse precursors such as hormone e.g., procalcitonin.

Classification and clinical effects of amyloidosis:

Amyloidosis is classified according to the clinical and chemical features into:
Primary amyloidosis or the immunocytes derived amyloidosis: The deposited protein here is derived from the light chain of Ig and has system distribution (In all organs). This type associates with plasma cell dyscrasias like multiple myeloma. The most affected organs are the heart, kidneys, GIT and others. The patient will suffer a gradual congestive heart failure, renal failure, proteinuria, diarrhea and malabsorption. The prognosis is poor.
Reactive systemic amyloidosis associates with chronic inflammation or chronic infections like T.B, Bronchiectasis, chronic osteomyelitis, Rheumatoid arthritis. The protein deposit is derived from the SAA protein. Renal involvement is prominent complication of this type. The prognosis depends on treatment of the underlying condition.
Endocrine amyloidosis is found in some conditions like medullary carcinoma of the thyroid gland and here the amyloid protein is derived from procalcitonin. Also in the pancreas in cases of Type II D.M.
Amyloidosis of aging: this is two types:
A: Senile cardial amyloidosis usually occurs in the hearts of elderly patients (>80y.)
B: Senile cerebral amyloidosis in patients with Alzheimer's Disease.
Heredofamilial amyloidosis. As in familial Mediterranean fever and familial amyloid polyneuropathy.
Localized amyloidosis: seen in certain endocrine tumors, such as medullary carcinoma of the thyroid gland, islet tumor of the pancreas and in the islets of Langerhans in patients with type II DM.


Morphology:
Although immunocyte-associated amyloidosis cannot reliably be distinguished from the secondary form by its organ distribution, more often it involves the heart, kidney, GIT, peripheral nerves, skin & tongue.
Macroscopically the affected organs are often enlarged, firm & have a waxy appearance.
Heart
Histologically the deposits begin in focal subendocardial accumulation & within the myocardium between muscle fibers leading to pressure atrophy of myocardial fibers.
Kidney
Histologically the amyloid is deposited primarily in the glomeruli, lead to thickening of the mesangial matrix with widening of the basement membrane, it also deposited in the interstitial peritubular tissue, arteries & arterioles.
Spleen
Amyloidosis is limited to the splenic follicles leading to Sago spleen.
Amyloidosis limited to the red pulp leading to Lardaceous spleen
Liver
Amyloidosis appears first in the space of Disse and then progressively enlarge to encroach on the adjacent hepatic parenchyma and sinusoids lead to pressure atrophy.
G.I.T
May be involved at any level from oral cavity to anus .
The early lesion mainly affect blood vessels but eventually extent to involved the adjacent areas of the submucosa ,muscularis & subserosa.

Diagnosis

Diagnosis of amyloidosis is by taking a biopsy from kidney, gingival, rectum, skin, or omental fat and stain it by a special stain for amyloidosis. With the light microscope and H &E stain, amyloid appears as an amorphous, eosinophilic hyaline extra cellular substance
To differentiate amyloid from other hyaline deposits (e.g. collagen, fibrin), a variety of histochemical techniques used. Perhaps most widely used is the Congo red stain, which under ordinary light imparts a pink or red color to amyloid deposits. Under polarized light, the Congo red -stained amyloid shows a green birefringence. Confirmation can be obtained by electron microscopy, by which amyloid is seen to be made up largely of non-branching fibrils of indefinite length and a diameter of approximately 7.5 - 10 nm. This electron microscopic structure is identical in all types of amyloidosis.