Characterisation

 

Clinical assessment of the type of amyloid

After confirmation of the presence of amyloid in tissue the next step must be assessment of the type of amyloid involved. In many instances history, complaints, and clinical picture provide enough information to get a reliable idea of the type of amyloid. Amyloid detected in a patient with longstanding rheumatoid arthritis and a nephrotic syndrome is almost undoubtedly AA type. Someone with polyneuropathy and amyloid who belongs to a family with heritable ATTR amyloidosis most likely will have ATTR type. And a patient with amyloid and clinical signs such as shoulder pads and glossomegaly most likely will have AL type. But even in these cases further proof of the particular type involved is mandatory. The way of treatment of the different systemic types of amyloidosis differs so much that definite proof of the type of amyloid should be aimed for.

Characterising the type of amyloid

Immunohistological investigation of a biopsy offers the possibility to characterise the type of amyloid by using specifically developed antibodies directed against particular amyloid proteins. In AA amyloidosis this immunohistology is sufficient, provided that sensitive and specific monoclonal antibodies are used. However, in many cases of AL and ATTR amyloidosis this method does not give unequivocal results because of less specific antibodies and a decreased recognition of antigenic epitopes of the precursor protein within the amyloid deposits. The clinical presentation of AL and ATTR amyloidosis can overlap considerably, such as in case of polyneuropathy, autonomic neuropathy, cardiomyopathy, and carpal tunnel syndrome (CTS). The absence of a family history for amyloid does not exclude hereditary amyloid such as ATTR type, because many cases seem to occur sporadically but are indeed familial. Therefore in hereditary amyloidosis such as ATTR type the presence of a mutation must be shown by DNA analysis. In AL amyloidosis a monoclonal plasma cell dyscrasia needs to be shown present in bone marrow (by immunophenotyping) or the monoclonal free kappa or lambda light chains (by immunofixation of blood or concentrated urine or by the recently described free light chain test). Even if such a monoclonal plasma cell dyscrasia is present in some cases it is good to exclude mutations of TTR or other amyloidogenic proteins. For completeness it is illustrative (but not proving) to show elevated serum levels of acute phase proteins (such as CRP and the precursor protein SAA) in AA amyloidosis. The same is true for ATTR amyloidosis in which the mutated TTR can be detected in the blood by immunoelectric focusing.

In complicated cases in which the amyloid type cannot precisely be determined consultation can take place with specialised institutions abroad.

 

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Publications of our group:

 

Janssen S, Elema JD, van Rijswijk MH, Limburg PC, Meijer S, Mandema E. Classification of amyloidosis: immunohistochemistry versus the potassium permanganate method in differentiating AA from AL amyloidosis. Appl Pathol 1985; 3(1-2):29-38

van Rijswijk MH, van Heusden CW. The potassium permanganate method. A reliable method for differentiating amyloid AA from other forms of amyloid in routine laboratory practice. Am J Pathol 1979; 97(1):43-58