Amyloidosis is a rare condition caused by extracellular deposition of misfolded proteins accumulated in the extracellular tissues of the body that may lead to impairment of organ function. To date, there are more than 30 different proteins known to cause amyloidosis. Clinically, the most important amyloidogenic proteins are serum amyloid A (SAA), transthyretin (TTR), and immunoglobulin kappa or lambda light chains (AL amyloidosis). They account for more than 90% of systemic amyloidosis.
Correct identification of the causal amyloid protein is absolutely crucial for clinical management in order to avoid misdiagnosis and consequently inappropriate, potentially harmful treatment (like chemotherapy, peripheral blood autologous stem cell transplantation, solid organ transplantation), to assess prognosis, and to offer genetic counseling if relevant. Moreover, several targeted emergent treatments are currently available.
Therefore, accurate subtyping of amyloid deposits is of paramount importance.
In routine practice, the diagnosis is made on tissue specimens using Congo red staining. After diagnosis, subtyping is commonly performed with immunohistochemistry, but, this method has low specificity and sensitivity.
To overcome these difficulties, a method relying on mass spectrometry-based proteomics has been successfully developed reaching an accurate typing in 94% of cases. Interestingly, this method does not require large amount of amyloid deposits and could be achieved from routine paraffin-embedded tissue. Mass spectrometry-based proteomics is now recognized as the gold standard for classification of amyloidosis. Moreover, it has been demonstrated that this technique is also a reliable tool for the diagnosis of amyloidosis related disorders like Light Chain Deposition Disease (LCDD).