Current Standards and Perspectives in Proteomics for Cardiac Amyloidosis

Area of Science:

• Biochemistry
• Pathology
• Medical Diagnostics

Background:

• Amyloidosis involves protein misfolding and deposition, leading to organ dysfunction.
• Cardiac amyloidosis, particularly transthyretin (ATTR) and immunoglobulin light chain (AL) types, significantly impacts prognosis and treatment.
• Tissue biopsy is currently essential for diagnosing amyloidosis, with histological typing via antibody-based methods.

Purpose of the Study:

• To describe the current application of mass spectrometry-based proteomics for amyloid typing in cardiac amyloidosis.
• To provide guidance on enhancing the reliability and standardization of proteomics in clinical workflows.
• To identify current challenges and gaps in the clinical use of proteomics for amyloidosis typing.

Main Methods:

• Review of proteomics application in cardiac amyloidosis patients from US and European referral centers.
• Focus on mass spectrometry-based bottom-up proteomics for identifying and quantifying amyloidogenic proteins.
• Comparison with traditional antibody-based histological typing methods.

Main Results:

• Proteomics provides precise identification and quantification of amyloidogenic proteins, serving as a powerful alternative to traditional methods.
• Current application of proteomics is limited to specialized centers due to technical complexity and lack of standardization.
• Significant potential exists for improving the technique's reliability and establishing standard clinical practices.

Conclusions:

• Proteomics is a valuable tool for accurate amyloid typing in cardiac amyloidosis.
• Standardization and addressing technical complexities are crucial for broader clinical adoption.
• Further development is needed to bridge the gap between specialized use and routine clinical application.