Identification of the EGF-TM7 receptor EMR2 and its ligand dermatan sulphate in rheumatoid synovial tissue

EMR2 is a member of the EGF-TM7 family closely related to CD97. Chondroitin sulphates have recently been identified as ligands for EMR2 and CD97. Chondroitin sulphates have been implicated in the pathogenesis of rheumatoid arthritis (RA). The objective of this study is to determine the expression of EMR2 and the distribution of EMR2 and CD97 ligands in RA synovial tissue.

Synovial tissue samples were obtained by arthroscopy from patients with RA (n = 19), inflammatory osteoarthritis (n = 13), and reactive arthritis (n = 13). Immunohistologic staining was performed with EMR2 mAb and stained synovial tissue sections were analysed by digital image analysis. Co-expression of EMR2 with lineage and activation markers was determined by double immunofluorescence microscopy. To evaluate the expression of EMR2 and CD97 ligands in RA synovium, binding assays using fluorescent beads loaded with EMR2-Fc or CD97-Fc constructs were performed.

EMR2 expression in the synovial sublining was significantly higher in RA compared with disease controls. Most EMR2-positive cells were macrophages and dendritic cells, expressing co-stimulatory molecules and tumour necrosis factor alpha. Dermatan sulphate was shown to be the ligand of the largest isoform of EMR2 and CD97 in rheumatoid synovium. In addition, the smaller isoforms of CD97, but not EMR2, bound CD55 on fibroblast-like synoviocytes.

The EGF-TM7 receptor EMR2 and CD97 are abundantly expressed on myeloid cells in synovial tissue of RA patients where they encounter their ligands dermatan sulphate and CD55. These interactions might facilitate the retention of activated macrophages in the synovium.

Affiliations

1. Division of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands
   • EN Kop
   • , GJD Teske
   • , MC Kraan
   • , TJ Smeets
   •  & PP Tak
2. Laboratory of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands
   • MJ Kwakkenbos
   •  & J Hamann
3. Sir William Dunn School of Pathology, University of Oxford, UK
   • M Stacey
   •  & H-H Lin

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