Description:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 ∼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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>