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Immunohistochemical detection of advanced glycation end products in dialysis-related amyloidosis
T Niwa1, S Miyazaki, T Katsuzaki
1Nagoya University Branch Hospital, Japan.
Abstract:
beta 2-Microglobulin (beta 2m) isolated from the amyloid deposits in patients with dialysis-related amyloidosis (DRA) has been demonstrated to be modified with advanced glycation end products (AGE). We produced a monoclonal anti-AGE antibody which localized AGE to amyloid deposits in patients with DRA by immunohistochemistry. The connective tissues in the carpal tunnel were obtained from surgical specimens in six patients with DRA. AGE were localized to the beta 2m-positive amyloid deposits in these patients using the monoclonal anti-AGE antibody. AGE were also detected in infiltrating cells surrounding the amyloid deposits. The AGE-positive cells were identified as macrophages, since they showed positive staining with anti-CD68 antibody. In conclusion, AGE were demonstrated by immunohistochemical technique to be present in both beta 2m-positive amyloid deposits and surrounding macrophages in patients with DRA.
Insights
Advanced glycation end products (AGE) modify beta 2-microglobulin (beta 2m) in dialysis-related amyloidosis (DRA). These AGEs are present in both beta 2m amyloid deposits and surrounding macrophages in DRA patients.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Dialysis-related amyloidosis (DRA) involves beta 2-microglobulin (beta 2m) amyloid deposition.
- Advanced glycation end products (AGE) are implicated in protein modification and tissue damage.
Purpose of the Study:
- To investigate the presence and localization of AGE in beta 2m amyloid deposits and associated cells in patients with DRA.
- To characterize the cellular infiltrate in the amyloid deposits of DRA patients.
Main Methods:
- Production of a monoclonal anti-AGE antibody.
- Immunohistochemical analysis of carpal tunnel connective tissues from DRA patients.
- Staining for beta 2m, AGE, and CD68 (a macrophage marker).
Main Results:
- AGEs were localized to beta 2m-positive amyloid deposits in DRA patient tissues.
- AGEs were also detected in infiltrating cells surrounding the amyloid deposits.
- These AGE-positive cells were identified as macrophages.
Conclusions:
- Advanced glycation end products (AGE) are present in beta 2m amyloid deposits in dialysis-related amyloidosis.
- Macrophages infiltrating the amyloid deposits also contain AGEs.
- This suggests a role for AGE modification and macrophage involvement in the pathogenesis of DRA.