Immunohistochemical localization of amyloid in Finnish hereditary amyloidosis with antibodies to gelsolin peptides.

The amyloid fibril protein in the Finnish type of familial amyloid polyneuropathy was recently identified as a fragment of gelsolin, a cytoskeletal and plasma protein with actin-modulating properties. Antibodies to three synthetic peptides of various parts of gelsolin were raised in rabbits and used in immunocytochemistry. The P-3 dodecapeptide, corresponding to the C-terminal region of the amyloid protein, elicited the best immunologic response and the P-3 antibodies were found suitable for use in immunohistochemistry and enzyme immunoassay. The P-3 antibodies specifically stained the amyloid deposits in various tissues including the skin, kidney, heart, thyroid gland, salivary gland, and rectum in patients with Finnish familial amyloid polyneuropathy. The staining was completely abolished by absorption of the antiserum with the synthetic dodecapeptide used for immunization, but not by a peptide of another region of the gelsolin molecule. The antibodies did not stain the amyloid of secondary amyloid A or of the myeloma-associated amyloid light chain. The results provide evidence for the relation between the amyloid deposited in the systemic tissues of patients with Finnish familial amyloid polyneuropathy and gelsolin, and demonstrate the utility of these anti-gelsolin antibodies in diagnostic immunohistochemistry.