Keskin Derin B, Stern Joel N H, Fridkis-Hareli Masha, Razzaque Ahmed A
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA, USA.
Cytokine. 2008 Mar;41(3):315-21. doi: 10.1016/j.cyto.2007.12.007.
Pemphigus vulgaris (PV) is a potentially fatal blistering disease of the skin and mucous membranes, characterized by the presence of autoantibodies against adhesion molecules (desmoglein, Dsg3) present on the surface of keratinocytes, which lead to the loss of cellular adhesion or acantholysis. The mainstay of treatment is conventional immunosuppressive therapy (CIST), i.e. high dose, long-term systemic corticosteroids with or without immunosuppressive drugs. Intravenous immunoglobulin (IVIg) has been used in patients refractory to CIST, and its use has resulted in long-term clinical remission. Since cytokines play an important role in the immunopathogenesis of PV, it would be useful to compare how both IVIg and CIST therapies affect cytokine levels in the serum of PV patients. Thus, the goal of this study was to conduct a comparative analysis of levels of various cytokines, during an 18 month consecutive period, after the initiation of CIST or IVIg treatment in PV patients, with similar extent and severity of disease in the two study groups, with 11 patients in each group. The cytokines measured were IL-1beta, IL-6, IL-8, IFN-gamma, IL-4 and IL-10. The levels of most of these cytokines were higher in the sera of untreated patients in both groups, compared to normal controls. The cumulative data collected over an 18 month period of treatment demonstrates that there is a gradual reduction in the levels of these cytokines, until they are at levels observed in normal individuals. The conclusions from this limited number of patients, prospectively studied, would suggest that both CIST and IVIg therapies are similar in their ability to influence a panel of cytokines in patients with pemphigus vulgaris.
寻常型天疱疮(PV)是一种潜在致命的皮肤和黏膜水疱性疾病,其特征是存在针对角质形成细胞表面黏附分子(桥粒芯糖蛋白,Dsg3)的自身抗体,这些抗体会导致细胞黏附丧失或棘层松解。治疗的主要方法是传统免疫抑制疗法(CIST),即高剂量、长期使用全身性皮质类固醇,可联合或不联合免疫抑制药物。静脉注射免疫球蛋白(IVIg)已用于对CIST难治的患者,其使用已导致长期临床缓解。由于细胞因子在PV的免疫发病机制中起重要作用,比较IVIg和CIST疗法如何影响PV患者血清中的细胞因子水平将是有益的。因此,本研究的目的是在18个月的连续期间内,对PV患者开始CIST或IVIg治疗后,对各种细胞因子水平进行比较分析,两个研究组的疾病程度和严重程度相似,每组各有11名患者。所检测的细胞因子为IL-1β、IL-6、IL-8、IFN-γ、IL-4和IL-10。与正常对照组相比,两组未治疗患者血清中大多数这些细胞因子的水平更高。在18个月治疗期间收集的累积数据表明,这些细胞因子的水平逐渐降低,直至达到正常个体中观察到的水平。对这一有限数量患者进行前瞻性研究得出的结论表明,CIST和IVIg疗法在影响寻常型天疱疮患者一组细胞因子的能力方面相似。