ABSTRACT
The available data on the pathophysiology of beta(2)-microglobulin amyloidosis (beta(2)mA) suggest that this progressive disease associated with end-stage renal failure develops in several consecutive phases. First, declining kidney function leads to retention of beta(2) microglobulin (beta(2)m) 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 beta(2)m, takes place. Deposition and fibril formation occur in the absence of modification of beta(2)mA 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 beta(2)m induces a local inflammatory response by attracting macrophages chemotactically and by stimulating these cells to produce and release proinflammatory cytokines. In addition, unmodified beta(2)m 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 beta(2)mA.
