Amyloid Protein Identification

March 2011

Overview

Amyloidosis is a disease characterized by abnormal deposition of cellular proteins in extracellular sites in a physical form that is resistant to normal degradation processes. The disease is often systemic and life threatening, frequently affecting vital organs such as the kidneys or the heart. At least 25 different proteins have been shown to cause amyloidosis, and the underlying pathogenesis of each subtype of amyloidosis is unique.

Useful For

• Test: Amyloid Protein Identification, Paraffin, LC MS/MS (82091)
  Identifying proteins involved in amyloidosis

• Hot Topic: Diagnosis and Classification of Amyloidosis

  Ahmet Dogan, MD, PhD, Medical Director of the Immunostains Laboratory in the Division of Anatomic Pathology, Mayo Clinic

• Algorithm: Laboratory Approach to the Diagnosis of Amyloidosis

Mayo Clinic has developed a novel diagnostic methodology that can subtype amyloidosis in routine biopsy specimens with high accuracy. The method combines specific sampling of the amyloid plaques by laser microdissection (LMD) and the analytical power of tandem mass spectrometry (MS)-based proteomic analysis.

The management of amyloidosis is based on treatment of the underlying cause of abnormal deposition of proteins in extracellular sites and the treatment approaches for different subtypes of amyloid may be radically different. For example, AL amyloidosis may be treated by high dose chemotherapy and stem cell transplantation whereas hereditary ATTR amyloidosis may be treated by liver transplantation. Given the risks associated with amyloidosis and different types of treatment, accurate subtyping of amyloidosis is of paramount importance for timely, effective and cost efficient disease management. This test can guide treatment decisions that range from basic monitoring to organ transplant.

Test Results and Consultations

In the clinical validation set, the LMD/MS method identified the amyloid type with 100% specificity and sensitivity (1). This provides a major improvement on previous widely used methods such as immunohistochemistry, which provides lower sensitivity and specificity (40-80%).

This test is only available at Mayo Clinic.

Clinical References

1. Vrana JA, Gamez JD, Madden BJ, et al: Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens. Blood 2009;114(24):4957-4959
2. Rodriguez FJ, Gamez JD, Vrana JA, et al: Immunoglobulin derived depositions in the nervous system: novel mass spectrometry application for protein characterization in formalin-fixed tissues. Lab. Invest. 2008;88(10):1024-1037
3. Picken MM: New insights into systemic amyloidosis: the importance of diagnosis of specific type. Curr Opin Nephrol Hypertens 2007;16:196-203
4. Dispenzieri A, Gertz MA: The laboratory diagnosis and monitoring of amyloidosis. Communique 2002;27(9):1-10