Expression of myeloid-related proteins 8 and 14 in systemic-onset juvenile rheumatoid arthritis.
OBJECTIVE: To analyze which cellular compartments are involved in the initial phase of systemic-onset juvenile rheumatoid arthritis (JRA), and to investigate the role that myeloid-related protein 8 ( MRP-8) and MRP-14, two S-100 proteins that are primarily expressed in phagocytes, play in the disease. METHODS: Skin biopsy samples obtained during patients' acute episodes of systemic-onset JRA were analyzed by immunohistochemistry and in situ hybridization. Concentrations of MRP-8/MRP-14 in serum were determined by enzyme-linked immunosorbent assay. RESULTS: By analyzing biopsy samples from cutaneous rashes during the initial phase of systemic-onset JRA, we discovered infiltration of leukocytes expressing MRP-8 and MRP-14. Surprisingly, keratinocytes also showed de novo synthesis of these proinflammatory proteins, indicating activation of epithelial cells during systemic-onset JRA. Serum concentrations of MRP-8/MRP-14 were 120-fold higher compared with healthy controls and approximately 12-fold higher compared with patients with other inflammatory diseases. Concentrations of MRP-8/MRP-14 in patients with systemic-onset JRA fell dramatically after remission was induced. CONCLUSION: The exceptionally high serum levels of MRP-8 and MRP-14 in active systemic-onset JRA make them prime candidates as markers for monitoring disease activity and response to treatment. Since MRP-8/MRP-14 exhibit direct effects on leukocyte adhesion to the vascular endothelium, their extensive expression in the epidermis indicates an active role for these S-100 proteins in the initial phase of this systemic autoimmune disease.[1]References
- Expression of myeloid-related proteins 8 and 14 in systemic-onset juvenile rheumatoid arthritis. Frosch, M., Vogl, T., Seeliger, S., Wulffraat, N., Kuis, W., Viemann, D., Foell, D., Sorg, C., Sunderkötter, C., Roth, J. Arthritis Rheum. (2003) [Pubmed]
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