Ghaiad Heba R, Elmazny Alaa N, Nooh Mohammed M, El-Sawalhi Maha M, Shaheen Amira A
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Neurology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
J Adv Res. 2019 Nov 4;21:141-150. doi: 10.1016/j.jare.2019.10.012. eCollection 2020 Jan.
Lately, long noncoding (lnc) RNAs are increasingly appreciated for their involvement in multiple sclerosis (MS). In inflammation and autoimmunity, a role of apoprotein A1 (ApoA1), mediated by sphingosine 1-phosphate receptors (S1PRs), was reported. However, the epigenetic mechanisms regulating these biomolecules and their role in MS remains elusive. This case control study investigated the role of ApoA1, sphingosine kinase 1 and 2 (SPHK1 & 2), S1PR1 & 5, interferon-γ (IFN-γ) and interleukin 17 (IL17) in MS, beside three lncRNA: APOA1-AS, IFNG-AS1, and RMRP. Expression of SPHKs, S1PRs, and lncRNAs were measured in 72 relapsing-remitting MS patients (37 during relapse and 35 in remission) and 28 controls. Plasma levels of ApoA1, IFN-γ and IL17 were determined. The impact of these parameters on MS activity, relapse rate and patient disability was assessed. APOA1-AS, IFNG-AS1, SPHK1 & 2, and S1PR5 were upregulated in RRMS patients. Differences in ApoA1, SPHK2, and IL17 were observed between relapse and remission. Importantly, ApoA1, SPHK2, and IL17 were related to activity, while S1PR1 and IFN-γ were linked to disability, though, only IFN-γ was associated with relapse rate. Finally, an excellent diagnostic power of IFN-γ, IL17, SPHK1 and APOA1-AS was demonstrated, whereas SPHK2 showed promising prognostic power in predicting relapses.
最近，长链非编码（lnc）RNA因其在多发性硬化症（MS）中的作用而越来越受到关注。在炎症和自身免疫中，有报道称载脂蛋白A1（ApoA1）通过1-磷酸鞘氨醇受体（S1PRs）发挥作用。然而，调节这些生物分子的表观遗传机制及其在MS中的作用仍不清楚。这项病例对照研究调查了ApoA1、鞘氨醇激酶1和2（SPHK1和SPHK2）、S1PR1和S1PR5、干扰素-γ（IFN-γ）和白细胞介素17（IL17）在MS中的作用，此外还研究了三种lncRNA：APOA1-AS、IFNG-AS1和RMRP。在72例复发缓解型MS患者（37例复发期和35例缓解期）和28例对照中测量了SPHKs、S1PRs和lncRNAs的表达。测定了血浆中ApoA1、IFN-γ和IL17的水平。评估了这些参数对MS活动、复发率和患者残疾的影响。RRMS患者中APOA1-AS、IFNG-AS1、SPHK1和SPHK2以及S1PR5上调。在复发期和缓解期观察到ApoA1、SPHK2和IL17的差异。重要的是，ApoA1、SPHK2和IL17与活动相关，而S1PR1和IFN-γ与残疾相关，不过，只有IFN-γ与复发率相关。最后，证明了IFN-γ、IL17、SPHK1和APOA1-AS具有出色的诊断能力，而SPHK2在预测复发方面显示出有前景的预后能力。
