The predilection for β2-microglobulin (β2M) amyloid deposition in articular structures is unique compared to other forms of amyloid; this article focuses on possible pathogenic mechanisms. The synovium and/or cartilage appear to be important in the pathogenesis of β2M amyloidosis (Aβ2M), as amyloid is not found in the shafts of long bones. The concentration of β2M in the joint fluid parallels that in serum. Once in the joint space, evidence suggests that the β2M binds to collagen in cartilage as the initial site of deposition. This binding may serve as the first step in subsequent amyloid formation, although this remains to be proven. β2M has been shown to have many direct effects on synovial fibroblasts, including induction of the release of cytokines, metalloproteinases, cyclooxygenase-2, and vascular cell adhesion molecule-1 (VCAM-1). The release of these inflammatory mediators that lead to tissue degradation is also observed in other forms of arthritis. Thus β2M itself may elicit the release of inflammatory mediators from synovial fibroblasts even in the absence of cellular infiltrates.
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