帕比司他对儿童系统性红斑狼疮患者培养淋巴细胞免疫抑制作用的体外评价

Neimat A Yassin, Maha Abdelsalam, Amr M El-Sabbagh, Amira I Morsy, Amira A Haleem, Ibrahim El-Shenbaby, Gehan A El Wakeel, Ayman Hammad, Nashwa Hamdy, Dena M Abd-El Ghafaar, Eman B Elmarghany, Mai S Korkor, Riham Eid
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摘要

虽然有许多药物可用于治疗儿童系统性红斑狼疮(SLE),但在某些情况下,不良反应和不良反应使得寻找针对疾病发病机制中各种途径的新药以改善总体预后至关重要。本研究旨在(i)研究Panobinostat对活动SLE儿童培养淋巴细胞的影响,(ii)将其与SLE使用的标准药物(如强的松和羟氯喹)的影响进行比较。研究纳入24例SLE活动期患者,分为4组。从研究患者的血液样本中分离淋巴细胞。实验组采用帕比诺他、强的松龙、羟氯喹或不处理(对照组)。细胞培养后,通过膜联蛋白V和碘化丙啶(PI)染色的流式细胞术检测淋巴细胞对药物治疗的反应,分析抗dsdna抗体的产生和细胞凋亡水平。Panobinostat组活细胞计数显著降低(p < 0.001)。泼尼松和羟氯喹均比帕比诺司他组和对照组更能降低抗dsdna表达(p < 0.001)。泼尼松组PI高于其他组,帕比诺他组Annexin V高于其他组;然而,他们的增加没有达到统计学显著水平(p分别= 0.12和0.85)。这是首次研究Panobinostat对SLE培养淋巴细胞的作用。总之,Panobinostat可能是b细胞驱动的自身免疫性疾病(如SLE)的前瞻性治疗方法。然而,其对自身抗体水平的影响以及SLE不同的临床特征仍需深入研究。
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In vitro evaluation of the potential immunosuppressive effect of panobinostat on cultured lymphocytes retrieved from childhood systemic lupus erythematosus patients
Although many drugs are available for childhood systemic lupus erythematosus (SLE) treatment, the adverse effects and poor response in some cases make it crucial to find new drugs targeting various pathways in disease pathogenesis to improve overall outcomes. This study aimed to (i) investigate the effect of Panobinostat on cultured lymphocytes obtained from children with active SLE and (ii) to compare that effect with standard drugs used in SLE, such as Prednisone and hydroxychloroquine. The study included 24 SLE active patients, divided into four equal groups. Lymphocytes were isolated from blood samples of the study patients. According to the study group, cells were treated with either Panobinostat, Prednisolone, hydroxychloroquine, or not treated (control group). After cell culture, the response of lymphocytes upon drug treatment was analyzed in terms of the production of anti-dsDNA antibodies and levels of apoptosis as detected by flow cytometry using annexin V and propidium iodide (PI) staining. The Panobinostat group showed a significant decrease in the viable cell count (p < 0.001). Both Prednisone and hydroxychloroquine decreased anti-dsDNA expression more than the Panobinostat and control groups (p < 0.001 for both). PI was higher in the Prednisone group, and Annexin V was higher in the Panobinostat group compared to other groups; however, their increase did not reach statistically significant levels (p= 0.12 and 0.85, respectively). This is the first study of the Panobinostat effect on cultured lymphocytes of SLE. In conclusion, Panobinostat could be a prospective treatment for B-cell-driven autoimmune diseases such as SLE. However, its effect on autoantibodies levels and different clinical features of SLE still need a thorough evaluation.
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