Identification of the advanced glycation end products N(epsilon)-carboxymethyllysine in the synovial tissue of patients with rheumatoid arthritis.
BACKGROUND
Generation of advanced glycation end products (AGEs) is an inevitable process in vivo and can be accelerated under pathological conditions such as oxidative stress. In serum and synovial fluid of patients with rheumatoid arthritis (RA) raised AGE levels have been found.


OBJECTIVE
To determine the presence of N(epsilon)-carboxymethyllysine (CML; marker of oxidative stress) in RA synovial tissue by immunohistology.


METHODS
Frozen synovial tissue samples from 10 patients with RA and eight controls (four patients without joint disease and four patients with osteoarthritis (OA)) were treated with rabbit-anti-CML-IgG and goat-antirabbit-IgG. Immunostaining was visualised by streptavidine-alkaline phosphatase (chromogen fuchsin). Cell differentiation was performed with antibodies against CD68, CD45RO, and CD20.


RESULTS
CML was detected in the synovial lining, sublining, and endothelium in 10/10 RA and 4/4 OA synovial specimens. In RA some macrophages (CD68+) and T cells (CD45RO+) showed positive immunostaining for CML, whereas B cells were negative. Staining in OA synovial sublining was weak compared with RA.


CONCLUSIONS
CML was detected for the first time in RA and OA synovial tissue. Different patterns of immunostaining in RA and OA and the presence of CML on macrophages and T cells, suggest a role for CML in the pathogenesis of RA. This might be due to presentation of new epitopes which can maintain or even trigger an autoimmune response.
Drinda
S
S
Department of Internal Medicine IV, Friedrich Schiller University Jena, Germany. stefan.drinda@med.uni-jena.de
Franke
S
S
Canet
C C
CC
Petrow
P
P
Bräuer
R
R
Hüttich
C
C
Stein
G
G
Hein
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D001402:B-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D017127:Glycation End Products, Advanced / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008239:Lysine / Q000031:analogs & derivatives / Q000032:analysis*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology; D013583:Synovial Membrane / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D017127:Glycation End Products, Advanced; C048496:N(6)-carboxymethyllysine; D008239:Lysine