LOCALIZED LARYNGEAL AMYLOIDOSIS: PA RTIA L CHARACTERIZATION OF AN AMYLOID FIBRIL PROTEIN AL PER WESTERMARK.*t KNUT SLETTEN,$ PETER PITK;d;NEN.* JA COB B. NATVIQ and CARL-ERIC LINDHOLM , Departments of Pathology* and Otolaryngology.~~ Llnivrrsity of Uppsala, Sweden: and Institute of Bi0chemistry.j University of Oslo: and Institute of Immunology and Rheumatology,\\ Rlkshospitalet Llniversity Hospital, Oslo. Norway Abstract ~Amyloid fibrils were extracted from a patient Wr with more than 10 yr history of localized laryngeal amyloidosis. Degraded amyloid fibrils reacted in immunodiffusion with an antiserum against an amyloid protein of lmmunoglobulin A- light chain origin. showing a line of identity with a ~1 amyloid protein. The protein Wr had a blocked aminoterminal. previously only reported in i chains. Amino acid sequence analysis of a fragment of the protein showed it to be an immunoglobulin light chain protein of VKI or VKIII subgroup. The protein had a few unusual ammo acid residues as compared to other K light chains. The findings support the view that the fibrils in localized. tumour-like amyloidosis are composed by homogeneous immunoglobulin light chain proteins in the same way as is seen in primary and myeloma associated systemic amyloidosis. It is possible that unusual light chams are over-represented zyxwvutsrqponm in a m ylo id fib rils INTRODUCTION Amyloid ccnsists mainly of thin. rigid fibrils. During the last 10 yr we have got an increasing knowledge about the chemical nature of the amyloid fibrils. A limited number of proteins have hitherto been shown to participate in the formation of the fibrils. In idiopathic (primary) systemic amyloidosis and in immunocytoma associated systemic amyloidosis, homogeneous immunoglobulin light chains and/or fragments thereof have been shown to be the major con- stituents of the fibrils (Glenner. 1980). Both K and 1. chains occur. Tumour-like. organ-limited amyloidosis is a rather rare condition that has been described in several areas in the body but mainly in the respiratory tract. the skin and the urinary blad- der. The disorder is usually not accompanied by any known plasma cell dyscrasia although amyloid depositions in plasmacytomas of the upper respiratory tract have been described (Michaels & Hyams, 1979). As far as known. localized amyloidosis is not followed by sys- temic disease. The morphology of the amyloid deposits in localized and tumour-like amyloi- dosis is indistinguishable from deposits seen in systemic amyloidosis but in the former con- tReprint requests to: P. Westermark, Department of Pathology. P.O. Box 553. S-751 13 Uppsala. Sweden. dition plasma cells are often seen in the peri- phery of the amyloid (Glenner et NI., 1973). It is possible that these cells represent a plasma cell dyscrasia and are the producers of the light chains that constitute the amyloid fibrils. Localized amyloidosis of the respiratory tract is most common in the larynx, where the deposits almost always are concentrated to the ventricular folds (Michaels & Hyams, 1979). In the present study we have analysed the major protein of amyloid fibrils, extracted from a patient with this type of localized amyloidosis. MATERIAL AND METHODS zyxwvutsrqponmlkji Short cme report A 53-yr-old man (Wr) had a known laryn- geal amyloidosis since more than 10 yr. The amyloidosis was localized to the ventricular folds. He had no signs of involvement of other parts of the respiratory tract. A subcutaneous fat tissue biopsy (Westermark & Stenkvist. 1973), which was performed to rule out sys- temic disease. was negative. A resection was performed and about 2 g of tissue, almost only consisting of amyloid, were immediately sent to the laboratory and kept at -20 C until processed. 441