Following staining and immunohistochemistry, Congo red-positive (amyloid) material is selected by laser capture dissection (LCD), and analysed by a proteomics approach using the Mascot search engine to identify the amyloidogenic protein(s). Variant and other searches are conducted as appropriate. The clinical and proteomic databases are linked, and we use a simple algorithm to automatically identify the pathogenic amyloid protein (3).
Amyloidogenic proteins identified in our patient database (3): apolipoproteins A1, A4, C2, C3, ANP, fibrinogen Aα chain, gelsolin, immunoglobulin light chains (lambda and kappa) and heavy chain, insulin, leukocyte cell-derived chemotaxin-2, lysozyme, b2-microglobulin, semenogelin, serum amyloid A, transthyretin.
Proteomics can also identify non-amyloid fibrillary glomerulonephritis from the DNJB9 signature (4).
Clinical proteomics data are reviewed, together with histological, genetic and clinical presentation, at a weekly multidisciplinary team meeting by both clinical and scientific research staff.
The NAC proteomics algorithm (3)