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ROCK1、RHOA 和 LIMK2 的 mRNA 水平作为与细胞凋亡相关的基因,可评估阿达木单抗治疗的效果。

mRNA level of ROCK1, RHOA, and LIMK2 as genes associated with apoptosis in evaluation of effectiveness of adalimumab treatment.

机构信息

Department of Nutrigenomics and Bromatology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Jednosci 8 Street, 41-200, Sosnowiec, Poland.

Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Sosnowiec, Poland.

出版信息

Pharmacol Rep. 2020 Apr;72(2):389-399. doi: 10.1007/s43440-020-00068-4. Epub 2020 Mar 2.

DOI:10.1007/s43440-020-00068-4
PMID:32124389
Abstract

BACKGROUND

Psoriasis is a multifactorial autoimmune disease, which underlies the abnormalities of the apoptotic process. In cases of psoriasis and psoriatic arthritis, biological treatment is used. This study aimed to determine any changes in the expression of the genes associated with apoptosis in patients with psoriatic arthritis treated with adalimumab and to assess any phenotypic modifications based on changes in dermatological indexes.

METHODS

The study included 20 patients with psoriatic arthritis treated biologically and 20 healthy volunteers. The research material consisted of peripheral blood mononuclear cells (PBMCs) from which the total RNA was isolated. Changes in the gene expression were determined using oligonucleotide microarrays and RT-qPCR. The clinical condition was assessed based on selected indicators: PASI, BSA [%], DAS28, and DLQI, which were determined every 3 months.

RESULTS

There were changes in the expression of genes associated with apoptosis. Significant differences were found for ROCK1, RhoA, and LIMK2 expression profiles in PBMCs. At the initial stage of treatment, a decrease in the PASI and BSA rates was observed. At the later stages, the values of these indicators increased once again. There were correlations between the changes in these genes' expression and the dermatological markers.

CONCLUSION

Adalimumab influences the expression of genes related to apoptosis and the values of dermatological indicators of patients. Changes in the expression level of genes associated with apoptosis suggest that ROCK1, RhoA, and LIMK2 may be genes that can potentially be indicators of treatment effectiveness and lack of response to biological treatment.

摘要

背景

银屑病是一种多因素自身免疫性疾病,其基础是凋亡过程的异常。在银屑病和银屑病关节炎的情况下,使用生物治疗。本研究旨在确定接受阿达木单抗治疗的银屑病关节炎患者中与凋亡相关的基因表达是否发生变化,并根据皮肤学指标的变化评估任何表型改变。

方法

该研究纳入了 20 名接受生物治疗的银屑病关节炎患者和 20 名健康志愿者。研究材料包括外周血单核细胞(PBMCs),从中分离出总 RNA。使用寡核苷酸微阵列和 RT-qPCR 确定基因表达的变化。根据 PASI、BSA [%]、DAS28 和 DLQI 等选定指标评估临床状况,这些指标每 3 个月确定一次。

结果

与凋亡相关的基因表达发生变化。在 PBMCs 中,ROCK1、RhoA 和 LIMK2 的表达谱存在显著差异。在治疗的初始阶段,PASI 和 BSA 率下降。在后期,这些指标的值再次增加。这些基因表达变化与皮肤学标志物之间存在相关性。

结论

阿达木单抗影响与凋亡相关的基因表达和患者皮肤学指标值。与凋亡相关的基因表达水平的变化表明,ROCK1、RhoA 和 LIMK2 可能是潜在的治疗效果和对生物治疗无反应的指标基因。

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