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Cells surrounding haemodialysis-associated amyloid deposits are mainly macrophages
Abstract:
Dialysis-related amyloidosis is a type of amyloidosis which had beta 2-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 beta 2-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.
Insights
Dialysis-related amyloidosis involves beta 2-microglobulin deposits. This study reveals these amyloid deposits are surrounded almost exclusively by macrophages, not lymphocytes or granulocytes.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Dialysis-related amyloidosis (DRA) is a complication of long-term hemodialysis, characterized by beta 2-microglobulin deposition.
- The cellular components surrounding DRA amyloid fibrils have not been previously characterized.
Purpose of the Study:
- To investigate the cellular composition of amyloid deposits in patients with dialysis-related amyloidosis.
- To identify the types and proportions of immune cells associated with beta 2-microglobulin amyloid fibrils.
Main Methods:
- Immunoperoxidase labeling was performed on amyloid tissue specimens from seven hemodialysis patients.
- Monoclonal antibodies targeting leukocyte markers (CD3, CD14, CD68, CD4, CD8, CD45) were used for cell characterization.
Main Results:
- Amyloid deposits were found to be infiltrated by leukocytes, identified by CD45 marker.
- Over 91% of these leukocytes were CD68-positive macrophages.
- T-cells (CD3-positive) were virtually absent, with no lymphocytes or granulocytes detected.
Conclusions:
- Contrary to the view of amyloidosis as acellular, cells are present around beta 2-microglobulin amyloid fibrils.
- These surrounding cells are predominantly macrophages, suggesting a potential role in DRA pathogenesis.
- Further research is needed to elucidate the specific role of macrophages in beta 2-microglobulin amyloidosis and protein-cell interactions.