Cells surrounding haemodialysis-associated amyloid deposits are mainly macrophages

Abstract

Dialysis-related amyloidosis is a type of amyloidosis which has β₂-microglobulin as the major protein constituent and occurs predominantly in haemodialysis patients. Its prevalence is very high with increasing time on dialysis treatment and its pathogenesis is not completely understood. While remarkable progress has been made in the identification of the components of the deposits, there are no reports characterizing the cells surrounding the amyloid fibrils. To characterize the cellular composition of the amyloid material, specimens from seven patients treated by maintenance haemodialysis were studied with immunoperoxidase labelling using monoclonal antibodies to leukocytes (CD3, CD14, CD68, CD4, CD8, CD45). The results were very reproducible for the seven deposits assessed: Of the 182 ± 26 leukocytes/0.2 mm² of amyloid tissue expressing the 71.5–CD45 marker (common leukocyte), 91± 6 % were CD68 (KP1) positive (monocyte macrophage). No CD3-positive cells (T-cell marker) were found in six of the seven patients, with only 1.6% in the remaining one. The present study shows that although amyloidosis has classically been considered as an acellular pathology, clearly there are cells surrounding amyloid fibrils. Strikingly, these cells are almost exclusively macrophages; there are no lymphocytes or granulocytes. The putative role of macrophages in the pathogenesis of β₂-microglobulin amyloidosis remains to be established. However, the identification and quantitation of the cells surrounding the amyloid deposits may be important for subsequent studies to elucidate amyloid pathogenesis and particularly protein–cell interactions.