From patterns to proteins: Mass spectrometry comes of age in glomerular disease.

Laser capture microdissection and mass spectrometry (LCM/MS) is technique that involves dissection of glomeruli from paraffin embedded biopsy tissue, followed by digestion of the dissected glomerular proteins by trypsin, and subsequently mass spectrometry to identify and semi quantitate the glomerular proteins. LCM/MS has played a crucial role in the identification of novel types of amyloidosis, biomarker discovery in fibrillary glomerulonephritis, and more recently discovery of novel target antigens in membranous nephropathy. In addition, LCM/MS has also confirmed the role for complement proteins in glomerular diseases, including C3 glomerulopathy. LCM/MS is now widely used a clinical test and considered the gold standard for diagnosis and typing amyloidosis. For the remaining glomerular diseases, LCM/MS, has remained a research tool. In this review, we discuss the usefulness of LCM/MS in other glomerular diseases, particularly membranous nephropathy, deposition diseases and diseases of complement pathways, and advocate more routine use of LCM/MS at the present time in at least certain diseases such as membranous nephropathy for target antigen detection. We also discuss the limitations of LCM/MS, particularly, the difficulties faced from moving from a research-based technique to a clinical test. Nonetheless, the role of LCM/MS in glomerular diseases is expanding. Currently LCM/MS may be used to identify the etiology in certain glomerular diseases but in the future LCM/MS can play a valuable role in determining pathways of complement activation, inflammation, and fibrosis.