Amyloid precursors and amyloidosis in rheumatoid arthritis

Amyloidosis refers to the extracellular accumulation of amyloid fibrils, derived from a circulating precursor, in various tissue and organs. The most common form of amyloidosis worldwide is that which occurs secondary to chronic inflammatory disease, particularly rheumatoid arthritis. The precursor molecule is serum amyloid A (SAA), an acute phase reactant, which can be used as a surrogate marker of inflammation in many diseases. SAA has a number of immunomodulatory roles, can induce chemotaxis and adhesion molecule expression, has cytokine-like properties and can promote the upregulation of metalloproteinases. It enhances the binding of high density lipoprotein to macrophages and thus helps in the delivery of lipids to sites of injury for use in tissue repair. It is thus thought to be an integral part of the disease process. Moreover, elevated levels of SAA over time predispose to secondary amyloidosis. Pathogenic factors underlying this disease are outlined along with guidelines for diagnosis and management.