Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Mult Scler Relat Disord. 2021 Jan;47:102613. doi: 10.1016/j.msard.2020.102613. Epub 2020 Nov 2.
Acute and chronic inflammatory demyelinating polyradiculoneuropathies (AIDP and CIDP) are two immune-related conditions in the peripheral nervous system. In the current study, we assessed expression levels of Beta-secretase (BACE1), brain-derived neurotrophic factor (BDNF) and their antisense transcripts in the peripheral blood of AIDP and CIDP patients compared with age- and sex-matched controls to assess their potential as biomarkers for these conditions. Expressions of BACE1 and BACE1-AS were down-regulated in CIDP cases compared with controls (Ratios of mean expressions=0.01 and 0.03; P values= 1.07E-08, respectively). On the other hand, expressions of BDNF and BDNF-AS were up-regulated in CIDP cases compared with controls (Ratios of mean expressions=4.78 and 25.71; P values= 7.84E-03 and 2.66E-07, respectively). Expressions of BACE1 and BACE1-AS were lower in AIDP cases compared with controls (Ratios of mean expressions=0.00; P values= 6.92E-10 and 8.04E-10, respectively). While expression of BDNF was not different between AIDP cases and controls, expression of its antisense transcript was higher in total AIDP cases compared with total controls (Ratio of mean expression= 8.61, P value=3.69E-04). Expressions of BACE1-AS, BDNF and BDNF-AS were significantly higher in CIDP cases compared with AIDP cases (Ratios of mean expression=1.98, 3.49 and 2.99; P values=4.67E-02, 4.67E-04 and 8.94E-03 respectively). Expression levels of BACE1, BACE1-AS and BDNF-AS could distinguish AIDP and CIDP cases from healthy subjects. BACE1 had the best diagnostic values in differentiation of CIDP and AIDP cases from controls (AUC values=0.88 and 0.91, respectively). Combination of all genes enhanced the diagnostic power to 0.96, 0.97 and 0.97 for differentiation between CIDP/controls, AIDP/controls and all patients/controls, respectively. Taken together, these genes might be implicated in the pathogenesis of AIDP and CIDP and can be suggested as putative markers for these conditions.
急性和慢性炎症性脱髓鞘性多发性神经病(AIDP 和 CIDP)是周围神经系统中的两种与免疫相关的疾病。在本研究中,我们评估了 AIDP 和 CIDP 患者与年龄和性别匹配的对照组相比,β-分泌酶(BACE1)、脑源性神经营养因子(BDNF)及其反义转录本在外周血中的表达水平,以评估它们作为这些疾病生物标志物的潜力。与对照组相比,CIDP 病例中 BACE1 和 BACE1-AS 的表达下调(平均表达比值=0.01 和 0.03;P 值分别为 1.07E-08)。另一方面,与对照组相比,CIDP 病例中 BDNF 和 BDNF-AS 的表达上调(平均表达比值分别为 4.78 和 25.71;P 值分别为 7.84E-03 和 2.66E-07)。与对照组相比,AIDP 病例中 BACE1 和 BACE1-AS 的表达较低(平均表达比值分别为 0.00;P 值分别为 6.92E-10 和 8.04E-10)。虽然 AIDP 病例与对照组之间 BDNF 的表达没有差异,但总 AIDP 病例的 BDNF 反义转录本表达高于总对照组(平均表达比值=8.61,P 值=3.69E-04)。与 AIDP 病例相比,CIDP 病例中 BACE1-AS、BDNF 和 BDNF-AS 的表达显著升高(平均表达比值分别为 1.98、3.49 和 2.99;P 值分别为 4.67E-02、4.67E-04 和 8.94E-03)。BACE1、BACE1-AS 和 BDNF-AS 的表达水平可将 AIDP 和 CIDP 病例与健康受试者区分开来。BACE1 在区分 CIDP 和 AIDP 病例与对照组方面具有最佳诊断价值(AUC 值分别为 0.88 和 0.91)。所有基因的组合将诊断能力分别提高到 0.96、0.97 和 0.97,用于区分 CIDP/对照组、AIDP/对照组和所有患者/对照组。总之,这些基因可能与 AIDP 和 CIDP 的发病机制有关,并可作为这些疾病的潜在标志物。