What are the laboratory tests for Amyloidosis?

From the Guidelines

The most effective approach to diagnosing amyloidosis involves a combination of laboratory tests, including serum and urine protein electrophoresis, serum free light chain assay, and tissue biopsy, as recommended by the 2023 ACC expert consensus decision pathway 1. To diagnose amyloidosis, the following laboratory tests are typically included:

• Serum protein electrophoresis with immunofixation to detect monoclonal proteins
• Serum free light chain assay to measure kappa and lambda light chains, which are crucial for identifying AL amyloidosis
• Urine protein electrophoresis with immunofixation on a 24-hour collection to detect Bence Jones proteins
• Complete blood count, comprehensive metabolic panel, cardiac biomarkers, and coagulation studies to assess organ involvement Tissue biopsy remains the gold standard for definitive diagnosis, with Congo red staining showing characteristic apple-green birefringence under polarized light, and mass spectrometry-based analysis (LC-MS/MS) of the biopsy being the gold standard for tissue diagnosis, with a reported sensitivity of 88% and specificity of 96% 1. The diagnostic approach to AL amyloidosis should consider a patient's seemingly disparate constellation of signs/symptoms, including unexplained proteinuria, restrictive cardiomyopathy, peripheral neuropathy, hepatomegaly, or acquired factor X deficiency with coagulopathy, and should involve both demonstration of tissue amyloid deposits and evidence of a plasma cell dyscrasia 1. Initial screening should include serum protein electrophoresis with immunofixation and serum free light chain assay, and additional tests such as NT-proBNP and troponin T for cardiac involvement, liver function tests, creatinine and BUN for renal function, and a complete blood count to assess for anemia or other cytopenias, as recommended by the european myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias 1.

From the Research

Amyloidosis Labs

• Amyloidosis is a multi-system disease caused by fibrillary protein deposition, and its diagnosis is often delayed due to variable and non-specific manifestations 2.
• The main forms of amyloidosis are light chain (AL) amyloidosis and transthyretin-related ATTR amyloidosis, which has both sporadic and hereditary subtypes 2.
• The diagnostic algorithm for amyloidosis is complex and generally requires histological confirmation of the diagnosis, with the exception of cardiac ATTR amyloidosis, which can be diagnosed non-invasively with bone scintigraphy once a monoclonal gammopathy has been excluded 2.

Diagnostic Tests

• Confirmation of amyloidosis in tissue by biopsy and Congo red staining with characteristic green birefringence under polarized light is recommended 3.
• Electron microscopy of biopsy tissue and protein typing by mass spectrometry are also recommended for diagnosis 3.
• Measurement of serum free light chains and serum and urinary immunofixation are recommended for evaluation of a monoclonal plasma cell proliferative disorder 3.
• Demonstration of a monoclonal plasma cell proliferative disorder by clonal plasma cells in the bone marrow is suggested for diagnosis of AL-type amyloidosis 3.

Laboratory Findings

• Mass spectrometry-based proteomic analysis can determine the validity of tests to predict amyloid type 4.
• Serum and urine protein electrophoresis (SPEP and UPEP) with immunofixation electrophoresis (IFE) and free light chain immunoassay (FLC) can detect monoclonal gammopathy, but are not robust predictors of cardiac amyloid type 4.
• FLC assay is a better predictor of AL amyloid type than SPEP/UPEP/IFE, but still has limitations 4.

Imaging and Diagnosis

• Advancements in MRI and nuclear medicine have provided greater specificity for the diagnosis of amyloidosis involving the central nervous system and heart, potentially obviating the need for biopsy in certain circumstances 5.
• A combination of characteristic findings at non-invasive cardiac MRI and skeletal scintigraphy can be diagnostic for cardiac transthyretin amyloidosis in patients without an underlying plasma cell dyscrasia 5.