Pathological aspects of beta(2)-microglobulin amyloidosis

Abstract

Histology remains the gold standard to diagnose beta(2)-microglobulin amyloidosis (A beta(2)M). Two diagnostic criteria are required: positive Congo red staining with typical birefringence under polarized light and immunostaining of amyloid deposits with a labeled anti-beta(2)M antibody. A beta(2)M is preferentially located in the joints. Small deposits are also found in various organs, mainly the heart and gastrointestinal tract. Pathologic studies have demonstrated a high prevalence of articular A beta(2)M early in the course of hemodialysis and peritoneal dialysis, antedating clinical manifestations by several years. The stages of beta(2)M amyloid formation have been delineated: beta(2)M amyloid deposits first on the surface of the cartilage, in the absence of macrophages (stage 1), and subsequently involves capsules and synovia (stage 2), with eventual recruitment of macrophages around large beta(2)M amyloid deposits (stage 3). Clinical manifestations are likely associated with the inflammation observed in stage 3. The factors triggering the fibrillar precipitation of beta(2)M remain unknown. Macrophages do not play a role: their presence is the consequence rather than the cause of beta(2)M amyloid deposits. Several substances coprecipitated with beta(2)M amyloid have been incriminated: highly sulfated glycosaminoglycans such as chondroitin or keratan sulfate, antiproteases such as alpha(2)-macroglobulin, and apolipoprotein E. As yet, no definitive conclusion has been reached.