Nephrology Dialysis Transplantation, Vol 13, Issue 6 1465-1475, Copyright © 1998 by Oxford University Press
G Ehlerding, J Schaeffer, W Drommer, T Miyata, K Koch and J Floege
Background: Beta-2-microglobulin-associated
amyloidosis (AB2M) is a frequent complication of long-term dialysis
treatment. Uraemic retention of beta-2-microglobulin ({beta}2M)
apparently constitutes the basis for AB2M. However, it is unclear why
clinical manifestations are largely confined to osteoarticular tissues. It
has been speculated that synovial inflammatory changes, induced by uraemia
and/or dialysis therapy could predispose this tissue to amyloid deposition.
Methods: We investigated which local synovial
alterations preceded or paralleled amyloid deposition. Using
immunohistology we evaluated synovial leukocyte infiltration (B and T
lymphocytes, monocytes/macrophages), cell proliferation, fibroblast
activation (de novo expression of
&agr;-smooth-muscle actin) the expression of extracellular matrix
components (heparan sulphate proteoglycan collagen types I, II, IV), and
advanced glycation end-products (AGEs). Results:
Synovial AB2M was detected in 20 of 36 chronic peritoneal and haemodialysis
patients and none of eight non-uraemic controls. Notably non-AB2M synovial
amyloid was present in six additional dialysis and three control patients.
Cellular infiltration was largely restricted to patients with advanced AB2M
deposits. The infiltrates consisted mainly of macrophages and progressed
with increasing degrees of AB2M deposition. In advanced cases they
exhibited characteristics of foreign-body reaction. Other infiltrating
leukocyte types, altered cell proliferation, or fibroblast activation were
absent or uncommon in periarticular tissue of dialysis patients with and
without AB2M. Neither dialysis treatment nor the presence of AB2M deposits
appreciably altered the qualitative matrix composition in periarticular
tissue. AGEs were present in AB2M deposits, the extracellular synovial
matrix of dialysis patients (of both, patients with and without AB2M) and,
to a lesser degree, in synovia of controls.
Conclusions: These data suggest that, except for AGE
formation, alterations of none of the parameters assessed, and in
particular no inflammatory tissue alterations, precede periarticular AB2M.
Rather synovial tissue, possibly modified by AGEs, seems to have an
intrinsic propensity for amyloid deposition and inflammatory changes appear
to only arise secondary to amyloid deposition. Key
words: advanced glycation end-products; amyloidosis;
{beta}2-microglobulin; dialysis; immunohistology; lymphocytes;
macrophages
ORIGINAL ARTICLES
Alterations of synovial tissue and their potential role in the deposition of {beta}2-microglobulin-associated amyloid
Division of Nephrology 6840 Medizinische Hochschule, D-30623 Hannover, Germany; Department of Pathology, Hannover Veterinary School, Germany; Institute of Medical Sciences and Department of Medicine, Tokai University School of Medicine, Isehara, Japan; Corresponding author
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. D. O'Neill, N. X. Chen, M. Wang, R. Cocklin, Y. Zhang, and S. M. Moe Cellular uptake of {beta}2M and AGE-{beta}2M in synovial fibroblasts and macrophages Nephrol. Dial. Transplant., January 1, 2003; 18(1): 46 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Lonnemann and K. M. Koch {beta}2-Microglobulin Amyloidosis: Effects of Ultrapure Dialysate and Type of Dialyzer Membrane J. Am. Soc. Nephrol., January 1, 2002; 13(90001): S72 - 77. [Abstract] [Full Text] [PDF]
|
|