EXTENDED REPORT

Identification of the advanced glycation end products N-carboxymethyllysine in the synovial tissue of patients with rheumatoid arthritis

S Drinda¹, S Franke¹, C C Canet², P Petrow², R Bräuer², C Hüttich², G Stein¹, G Hein¹

¹ Department of Internal Medicine IV, Friedrich Schiller University Jena, Germany
² Institute of Pathology, Friedrich Schiller University Jena, Germany

Correspondence to:
Correspondence to:
Dr S Drinda, Friedrich Schiller Universität Jena, Klinik für Innere Medizin IV, Rheumatologie/Osteologie, Erlanger Allee 101, 07740 Jena, Germany;
stefan.drinda{at}med.uni-jena.de

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.

Keywords: advanced glycation end products; carboxymethyllysine; rheumatoid arthritis; synovial tissue; immunohistochemistry

Abbreviations: AGEs, advanced glycation end products; CML, N-carboxymethyllysine; IL, interleukin; OA, osteoarthritis; RA, rheumatoid arthritis; RAGE, receptor for AGEs; TNF, tumour necrosis factor ; TRX, thioredoxin

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Pullerits, R., d'Elia, H. F., Tarkowski, A., Carlsten, H. (2009). The decrease of soluble RAGE levels in rheumatoid arthritis patients following hormone replacement therapy is associated with increased bone mineral density and diminished bone/cartilage turnover: a randomized controlled trial. Rheumatology (Oxford) 48: 785-790 [Abstract] [Full Text]  
• Pullerits, R., Bokarewa, M., Dahlberg, L., Tarkowski, A. (2007). Synovial fluid expression of autoantibodies specific for RAGE relates to less erosive course of rheumatoid arthritis. Rheumatology (Oxford) 46: 1367-1371 [Abstract] [Full Text]  
• Hein, G., Wiegand, R., Lehmann, G., Stein, G., Franke, S. (2003). Advanced glycation end-products pentosidine and N{epsilon}-carboxymethyllysine are elevated in serum of patients with osteoporosis. Rheumatology (Oxford) 42: 1242-1246 [Abstract] [Full Text]