Experimental transmission of systemic AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice

Abstract

AA amyloidosis is a protein misfolding disease characterized by extracellular deposition of amyloid A (AA) fibrils. AA amyloidosis has been identified in food animals, and it has been postulated that AA amyloidosis may be transmissible to different animal species. Since the precursor protein of AA fibrils is serum amyloid A (SAA), which is an inflammatory acute phase protein, AA amyloidosis is considered to be associated with inflammatory diseases such as rheumatoid arthritis. Chronic diseases such as autoimmune disease and type 2 diabetes mellitus could be potential factors for AA amyloidosis. In this study, to examine the relationship between the induction of AA amyloidosis and chromic abnormalities such as autoimmune disease or type 2 diabetes mellitus, amyloid fibrils from mice, cattle, or chickens were experimentally injected into disease model mice. Wild-type mice were used as controls. The concentrations of SAA, IL-6, and IL-10 in autoimmune disease model mice were higher than those of control mice. However, induction of AA amyloidosis in autoimmune disease and type 2 diabetes mellitus model mice was lower than that in control mice, and the amount of amyloid deposits in the spleens of both mouse models was lower than that of control mice according to Congo red staining and immunohistochemistry. These results suggest that factors other than SAA levels, such as an inflammatory or anti-inflammatory environment in the immune response, may be involved in amyloid deposition.

Aggregation of Mouse Serum Amyloid A Protein Was Promoted by Amyloid-Enhancing Factors with the More Genetically Homologous Serum Amyloid A

“…AA amyloidosis (reactive, secondary), which is characterized by the accumulation and deposition of β-sheet-rich and non-branching amyloid fibrils, associates with a number of pathological conditions in which can be associated with a severe complication of chronic inflammatory and other inflammatory-related diseases [29][30][31][32]. During the occurrence and development of this disease, SAA protein plays an important role in AA amyloidosis.…”

Type 2 Diabetes Mellitus: a reciprocal mutual interaction with amyloidosis or a presentation of an isolated primary pancreatic amyloidosis?

“…Meanwhile, secondary amyloidosis has been shown to complicate chronic inflammatory autoimmune diseases [4] and chronic diseases such as autoimmune disease and T2DM have also been suggested to be potential factors for AA amyloidosis [5]. Thus, a reciprocal interaction may be also involved; several cases of insulin-derived localized amyloidosis have been reported like those mentioned in [6,7] and a case of primary systemic amyloidosis with the history of T2DM for nine years has also been recently described [8].…”