Underdiagnosed amyloidosis: amyloidosis of lysozyme variant.
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The histological distribution and ultrastructural findings were investigated in 52 amyloid-positive cases obtained from 80 F1 mice (32 males and 48 females) receiving 126 to 502 daily intraperitoneal injections of ferric nitrilotriacetic acid (Fe-NTA) resulting from reciprocal crossing of 20 parental mice receiving daily intraperitoneal injections of Fe-NTA for 5 months. Of 52 amyloidotic F1 mice 49 (94%) developed a moderate degree of amyloid deposits in the gastrointestinal tract. Moderate amounts of amyloid deposits were sporadically discernible in the lamina propria of the stomach pars glandularis, the duodenal mucosa, and to a lesser extent in that of the rectal mucosa. Electron microscopic observation revealed that macrophages adjacent to amyloid mass were radiating outward abundant bundles of non-branching amyloid fibrils from the cytoplasmic invaginations. In the cytoplasm of the macrophages there were occasionally acid phosphatase-positive lysosomes including amyloid fibrils measuring approximately 100 A in width. Moreover, it is discussed whether fibroblasts or fibroblast-like interstitial cells are involved in amyloid formation.
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Variant forms and post-translational modifications of transthyretin (TTR) can be identified by electrospray ionisation mass spectrometry (ESI-MS). The aim of the present study was to investigate thiol conjugation of transthyretin and it's relation to age and symptomatic amyloid disease in different populations of variant TTR carriers. Plasma samples from 70 individuals from Denmark, Argentina, Sweden and Japan, with 2 different TTR mutations were analysed. The percentage cysteine (Cys) conjugated wild and variant TTR were calculated from the corresponding peaks of the spectra, and multiple regression analysis was employed to disclose relationships between age, symptomatic amyloid disease and origin. Age, origin and presence of symptomatic disease, were found to be independent factors related to transthyretin conjugation. A higher percentage of conjugated to unconjugated TTR was disclosed in symptomatic, but not in asymptomatic carriers. In summary: Thiol conjugation of TTR is dependent on age and presence of symptomatic amyloid disease. Furthermore, it varies between different populations. Variant TTR is more susceptible to thiol conjugation than the wild type. Post-translational factors may be related to amyloid formation and/or toxicity.
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