β2-Microglobulin Amyloidosis

The available data on the pathophysiology of β2-microglobulin amyloidosis (β2mA) suggest that this progressive disease associated with end-stage renal failure develops in several consecutive phases. First, declining kidney function leads to retention of β2 microglobulin (β2m) and its deposition preferentially in the synovial tissue of bigger joints such as wrists, shoulders, and hips. Second, at the site of deposition, formation of unique amyloid fibrils, whose major component is β2m, takes place. Deposition and fibril formation occur in the absence of modification of β2mA by advanced glycoxidation end products and also in the absence of a local inflammatory response. It is later, in the third phase, that advanced glycoxidation end product modification of β2m induces a local inflammatory response by attracting macrophages chemotactically and by stimulating these cells to produce and release proinflammatory cytokines. In addition, unmodified β2m itself induces inflammatory activities such as upregulation of cyclooxygenase-2 and metalloproteinase-1. The severity of the local inflammation seems to determine the degree of the destructive processes in tissue and bone accompanying β2mA.