Abstract:
Psoriasis is a chronic, inflammatory skin disease characterized by a dysregulated immune response and systemic inflammation. Up to one-third of patients with psoriasis have psoriatic arthritis (PsA). Targeted treatment with antibodies neutralizing tumor necrosis factor (TNF) can ameliorate both diseases. We here explored the impact of long-term infliximab treatment on the composition and activity status of circulating immune cells involved in chronic skin and joint inflammation. Immune cells were analyzed by multicolor flow cytometry. We measured markers of immune activation in peripheral blood mononuclear cell (PBMC) populations in 24 infliximab-treated patients with psoriasis/psoriatic arthritis compared to 32 healthy controls. We observed a significant decrease in the frequency of both peripheral natural killer (NK) cells and their subset CD56dimCD16+ NK cells in PsA compared to healthy controls and patients with psoriasis. The latter had a strong positive correlation with PASI in these patients, while CD56brightCD16- NK cells were negatively correlated with PASI. In addition, we observed an upregulation of CD69+ intermediate CD14+CD16+ and CD69+ classical CD14+CD16- monocytes in PsA and increased activity of CD38+ intermediate CD14+CD16+ monocytes in patients with psoriasis. Compared to healthy controls, psoriasis patients demonstrated shifts of the three B cell subsets with a decrease in transitional CD27-CD38high B cells. Our exploratory study indicates a preserved pathophysiological process including continuous systemic inflammation despite clinical stability of the patients treated with infliximab.
摘要:
牛皮癣是一种慢性,以免疫反应失调和全身性炎症为特征的炎症性皮肤病。多达三分之一的银屑病患者患有银屑病关节炎(PsA)。用中和肿瘤坏死因子(TNF)的抗体进行靶向治疗可以改善两种疾病。我们在这里探讨了长期英夫利昔单抗治疗对慢性皮肤和关节炎症中循环免疫细胞的组成和活性状态的影响。通过多色流式细胞术分析免疫细胞。我们测量了24例英夫利昔单抗治疗的银屑病/银屑病关节炎患者与32例健康对照的外周血单核细胞(PBMC)群体中免疫激活的标志物。与健康对照和银屑病患者相比,我们观察到PsA中外周自然杀伤(NK)细胞及其亚群CD56dimCD16NK细胞的频率显着降低。在这些患者中,后者与PASI有很强的正相关,而CD56brightCD16-NK细胞与PASI呈负相关。此外,我们观察到银屑病患者PsA中CD69+中间CD14+CD16+和CD69+经典CD14+CD16-单核细胞的上调和CD38+中间CD14+CD16+单核细胞的活性增加。与健康对照相比,银屑病患者表现出三个B细胞亚群的变化,过渡性CD27-CD38高B细胞的减少。我们的探索性研究表明,尽管接受英夫利昔单抗治疗的患者临床稳定,但病理生理过程仍保持不变,包括持续的全身性炎症。