Increase in plasma concentration of ubiquitin in dialysis patients: Possible involvement in β2-microglobulin amyloidosis

Abstract

β 2-Microglobulin( β2-M) amyloidosis is a serious complication of dialysis therapy; however, its pathogenesis is still unclear. Recent studies have indicated that ubiquitin has amyloid enhancing factor activity, raising the possibility that ubiquitin plays a role in β2-M amyloidogenesis. In this study, synovial tissue from patients with long-term dialysis was examined immunohistochemically. The synovial tissue was labeled with anti-ubiquitin antibody, indicating co-deposition of ubiquitin with β2-M amyloid. To elucidate the involvement of plasma ubiquitin, we established a specific radioimmunoassay for ubiquitin. Using this method, we observed that the plasma concentration of ubiquitin-like immunoreactivity in dialysis patients was significantly higher than that in normal subjects. In chronic renal failure patients, the plasma concentration of ubiquitin-like immunoreactivity was also significantly higher than that in normal controls, which finding suggests that a reduction in renal clearance is, at least in part, responsible for the increased plasma concentration of ubiquitin. In dialysis patients, plasma concentrations of ubiquitin-like immunoreactivity in patients with carpal tunnel syndrome, one of the major symptoms of β2-M amyloidosis, were significantly higher than those in patients not exhibiting this syndrome. These results suggest a possible involvement of plasma ubiquitin in β2-M amyloidosis.