Quantitative enrichment of amyloid precursors refines mass spectrometry-based amyloidosis diagnosis.

INTRODUCTION

Amyloidosis typing is crucial to determine the best therapeutic strategy for patients. Since conventional histological techniques often fail, the identification of amyloid precursors by mass spectrometry has become the new standard. However, without quantification, selecting the amyloid precursor from proteins that may be ubiquitous under non-pathological conditions can be equivocal. Therefore, we quantified protein enrichment in amyloid deposits to improve amyloidosis typing.

METHODS

Protein enrichment was measured by extracted ion chromatogram-based label-free quantification by comparing a microdissected amyloid area to a non-amyloid area. We assessed the discrimination ability of candidate precursors with this approach compared to the two practiced identification methods.

RESULTS

As a proof of concept, we selected 9 cases including the most common amyloidosis subtypes, 6 typed by immunohistochemistry and 3 inconclusive by immunohistochemistry. Proteins associated with amyloid deposits were identified in all samples, confirming the pathology. Where the routine clinical mass spectrometric identification techniques allowed unambiguous conclusions for 3 of 9 cases, quantification of the enrichment ratio in amyloid deposits allowed unambiguous precursor selection in all cases.

CONCLUSION

Quantification of precursor enrichment in amyloid deposits is a promising optimization for amyloidosis typing, which should be studied in larger cohorts. Incorporated into routine clinical processes, it could improve patient care in difficult diagnostic situations.