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Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. 2002 June; 61(6): 488–492.
PMCID: PMC1754129

Identification of the advanced glycation end products N -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 -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.

Figure 1
RA synovial tissue showing CML-expression (red) in the lining layer, the subsynovial interstitium, and in endothelial cells (x20).
Figure 2
RA synovial tissue with macrophage, which shows double staining: CML (red) and CD68+ (brown) (x40).
Figure 3
RA synovial tissue with activated T cells, which shows double staining: CML (red) and CD45RO+ (black) (x40).
Figure 4
RA synovial tissue with follicle of B cells (brown staining). CML positive cells are organised outside the follicle (x20).
Figure 5
OA synovial tissue showing CML expression (red) in the lining layer, the subsynovial interstitium, and in endothelial cells (x20). Overall, fewer inflammation cells are present compared with RA tissue.

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