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炎症性周围神经疾病患者血液中 NF-κB 相关转录本的异常表达。

Abnormal expression of NF-κB-related transcripts in blood of patients with inflammatory peripheral nerve disorders.

机构信息

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Electrical Engineering, Sharif University of Technology, Tehran, Iran.

出版信息

Metab Brain Dis. 2021 Dec;36(8):2369-2376. doi: 10.1007/s11011-021-00778-5. Epub 2021 Aug 19.

DOI:10.1007/s11011-021-00778-5
PMID:34410580
Abstract

The NF-κB family includes some transcription factors which have important functions in the regulation of immune responses, therefore participating in the pathophysiology of inflammatory conditions such as peripheral neuropathies. We have quantified expression of a number of NF-κB-related transcripts in patients with Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) versus healthy subjects. These transcripts have been previously shown to be functionally related with this family of transcription factors. Expressions of ATG5, DICER-AS1, PACER, DILC, NKILA and ADINR have been increased in both CIDP and GBS patients compared with controls. However, expression of ATG5 was not different between female CIDP cases and female controls. Moreover, expression of PACER was not different between male GBS cases and male controls. Expression levels of CHAST and CEBPA were not different between patients and controls. Expression of none of the assessed genes was different between GBS and CIDP cases. Significant correlations have been revealed between expression amounts of NF-κB-related transcripts both among CIDP/ GBS patients and among controls except for NKILA/ATG5, ADINR/ATG5 and PACER/ATG5 and DICER-AS1/ATG5 pairs among controls whose expression levels have not been correlated. In the patient group, CEBPA/PACER, CHAST/PACER and CHAST/DICER-AS1 pairs had the most robust correlations (r = 0.94). Among controls, NKILA/ADINR pair had the most strong correlation (r = 0.78). ADINR and DICER-AS1 levels could differentiate CIDP cases from controls with 100% sensitivity and specificity. In differentiation of GBS cases from controls, these two transcripts had the AUC values of 0.99 and 1. Combination transcript levels of NF-κB-related transcripts similarly detects CIDP and GBS cases from healthy controls with 100% sensitivity and specificity. Therefore, NF-κB-related transcripts are possibly involved in the pathophysiology of inflammatory peripheral nerve disorders and can be used as diagnostic markers for these conditions.

摘要

NF-κB 家族包括一些转录因子,它们在免疫反应的调节中具有重要功能,因此参与外周神经病变等炎症性疾病的病理生理学。我们已经量化了格林-巴利综合征(GBS)或慢性炎症性脱髓鞘性多发性神经病(CIDP)患者与健康受试者相比,许多与 NF-κB 相关的转录本的表达。这些转录本先前已被证明与该转录因子家族具有功能相关性。与对照组相比,CIDP 和 GBS 患者的 ATG5、DICER-AS1、PACER、DILC、NKILA 和 ADINR 的表达均增加。然而,女性 CIDP 病例与女性对照组之间 ATG5 的表达没有差异。此外,男性 GBS 病例与男性对照组之间 PACER 的表达没有差异。患者与对照组之间 CHAST 和 CEBPA 的表达水平没有差异。评估的基因在 GBS 和 CIDP 病例之间的表达没有差异。除了 NKILA/ATG5、ADINR/ATG5 和 PACER/ATG5 以及对照组中未相关的 DICER-AS1/ATG5 对之间,CIDP/GBS 患者和对照组之间的 NF-κB 相关转录本的表达量之间均揭示了显著相关性。在患者组中,CEBPA/PACER、CHAST/PACER 和 CHAST/DICER-AS1 对具有最强的相关性(r=0.94)。在对照组中,NKILA/ADINR 对具有最强的相关性(r=0.78)。ADINR 和 DICER-AS1 水平可以以 100%的灵敏度和特异性将 CIDP 病例与对照组区分开来。在将 GBS 病例与对照组区分开来时,这两个转录本的 AUC 值为 0.99 和 1. 组合 NF-κB 相关转录本的水平同样以 100%的灵敏度和特异性将 CIDP 和 GBS 病例与健康对照组区分开来。因此,NF-κB 相关转录本可能参与炎症性周围神经病变的病理生理学,可作为这些疾病的诊断标志物。

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