Frosch Michael, Metze Dieter, Foell Dirk, Vogl Thomas, Sorg Clemens, Sunderkötter Cord, Roth Johannes
Institute of Experimental Dermatology, University of Münster, Germany.
Exp Dermatol. 2005 Apr;14(4):259-65. doi: 10.1111/j.0906-6705.2005.00271.x.
In biopsies of 16 patients (mean: 5.2 years) with acute systemic onset juvenile idiopathic arthritis (SOJIA), we analysed the initial cellular events during the characteristic cutaneous rash for composition of the infiltrate and for expression of activation markers on epithelial and endothelial cells. Despite the fleeting nature of the rash, there was a characteristic infiltration of neutrophils and monocytes, accompanied by a marked expression of endothelial adhesion receptors. In addition, we found a general activation of the cutaneous epithelium reflected by the expression of the pro-inflammatory S100-proteins - myeloid-related protein 8 (MRP8) and MRP14. In responders to therapy, follow-up biopsies showed a complete normalization of these inflammatory parameters, whereas non-responders presented with continuous signs of activation. In conjunction with the high level of epithelial activation, we detected an infiltrate of leucocytes within epithelium of sweat gland ducts during active SOJIA. Such a pattern has not been described for other inflammatory skin diseases nor did we find it in biopsies from nine patients with acute urticaria. It was accompanied by exclusive expression of MRP8, but not MRP14 by the secretory cells of sweat glands. Because MRP8 and MRP14, released by epithelial cells, exhibit pro-inflammatory effects on endothelial cells and leucocytes, the particular expression pattern of MRP8 and MRP14 in SOJIA is likely to represent a decisive early constitutive component in this inflammatory disease. Their differential expression further points to distinct roles of the individual molecules in inflammatory processes.
在16例(平均病程5.2年)急性全身起病型幼年特发性关节炎(SOJIA)患者的活检样本中,我们分析了特征性皮肤皮疹发作初期的细胞事件,以了解浸润细胞的组成以及上皮细胞和内皮细胞上激活标志物的表达情况。尽管皮疹具有短暂性,但仍有中性粒细胞和单核细胞的特征性浸润,并伴有内皮黏附受体的显著表达。此外,我们发现促炎S100蛋白——髓样相关蛋白8(MRP8)和MRP14的表达反映了皮肤上皮的普遍激活。在治疗有反应的患者中,随访活检显示这些炎症参数完全恢复正常,而无反应者则持续存在激活迹象。结合高水平的上皮激活,我们在活动期SOJIA患者的汗腺导管上皮内检测到白细胞浸润。这种模式在其他炎症性皮肤病中未见报道,在9例急性荨麻疹患者的活检样本中也未发现。它伴随着汗腺分泌细胞中MRP8的特异性表达,但没有MRP14的表达。由于上皮细胞释放的MRP8和MRP14对内皮细胞和白细胞具有促炎作用,SOJIA中MRP8和MRP14的特定表达模式可能代表了这种炎症性疾病中决定性的早期组成成分。它们的差异表达进一步表明了单个分子在炎症过程中的不同作用。