Frosch Michael, Vogl Thomas, Seeliger Stephan, Wulffraat Nico, Kuis Wietse, Viemann Dorothee, Foell Dirk, Sorg Clemens, Sunderkötter Cord, Roth Johannes
Institute of Experimental Dermatology and Department of Pediatrics, University of Münster, Münster, Germany.
Arthritis Rheum. 2003 Sep;48(9):2622-6. doi: 10.1002/art.11177.
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.
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.
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.
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.
分析全身型幼年类风湿关节炎（JRA）初始阶段涉及哪些细胞区室，并研究主要在吞噬细胞中表达的两种S-100蛋白——髓样相关蛋白8（MRP-8）和MRP-14在该疾病中的作用。
通过免疫组织化学和原位杂交分析全身型JRA患者急性发作期获取的皮肤活检样本。采用酶联免疫吸附测定法测定血清中MRP-8/MRP-14的浓度。
通过分析全身型JRA初始阶段皮肤皮疹的活检样本，我们发现表达MRP-8和MRP-14的白细胞浸润。令人惊讶的是，角质形成细胞也显示出这些促炎蛋白的从头合成，表明全身型JRA期间上皮细胞被激活。与健康对照相比，MRP-8/MRP-14的血清浓度高120倍，与其他炎症性疾病患者相比约高12倍。诱导缓解后，全身型JRA患者的MRP-8/MRP-14浓度急剧下降。
活动期全身型JRA患者血清中MRP-8和MRP-14水平异常高，使其成为监测疾病活动和治疗反应的主要标志物候选物。由于MRP-8/MRP-14对白细胞黏附于血管内皮有直接作用，它们在表皮中的广泛表达表明这些S-100蛋白在这种全身性自身免疫疾病的初始阶段发挥积极作用。
