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Background: Fractalkine expressed on endothelial cells mediates activation and adhesion of leucocytes expressing its receptor, CX3CR1. Soluble fractalkine exhibits chemotactic activity for leucocytes expressing CX3CR1. Objective: To determine the role of fractalkine and its receptor in systemic sclerosis (SSc) by assessing their expression levels in patients with this disease. Methods: The expression of fractalkine and CX3CR1 in the skin and lung tissues was immunohistochemically examined. Circulating soluble fractalkine levels were examined by enzyme linked immunosorbent assay (ELISA). Blood samples from patients with SSc were stained for CX3CR1 with flow cytometric analysis. Results: CX3CR1 levels on peripheral monocytes/macrophages and T cells were found to be raised in patients with diffuse cutaneous SSc. The numbers of cells expressing CX3CR1, including monocytes/macrophages, were increased in the lesional skin and lung tissues from patients with diffuse cutaneous SSc. Fractalkine was strongly expressed on endothelial cells in the affected skin and lung tissues. Soluble fractalkine levels were significantly raised in sera and were associated with raised erythrocyte sedimentation rates, digital ischaemia, and severity of pulmonary fibrosis. Conclusions: Up regulated expression of fractalkine and CX3CR1 cooperatively augments the recruitment of mononuclear cells expressing CX3CR1 into the affected tissue of SSc, leading to inflammation and vascular injury.

Dermatomyositis (DM) is a heterogeneous disease with varying degrees and time courses of skin eruptions, myositis and internal organ involvement.1 Increasing evidence has demonstrated that myositis-specific autoantibodies (MSAs) are closely associated with distinct clinical subsets.2 Recently, Betteridge et al 3 ,4 reported a novel MSA against small ubiquitin-like modifier activating enzyme (SAE) in DM patients. In this study, we detected this autoantibody in a Japanese DM cohort and assessed its clinical correlations. We screened 456 consecutive Japanese patients with DM (11 children, 445 adults); 373 fulfilled the criteria of Bohan and Peter5 ,6 and the remaining 83 fulfilled Sontheimer's criteria for clinically amyopathic DM (CADM).7 Controls included 62 patients with polymyositis, 108 with systemic lupus erythematosus, 433 with systemic sclerosis and 124 with interstitial lung disease (ILD) alone. The institutional review board approved the study protocol. Immunoprecipitation assays were performed as described.8 Protein A-agarose beads preincubated with sera were incubated with 35S-methionine-labelled or unlabelled K562 cell extracts. Immunoprecipitants were fractionated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, followed by autoradiography or …