Comparison of OX40 expression in patients with multiple sclerosis and neuromyelitis optica as an approach to diagnosis.

Mostafa Manian, Morteza Motallebnezhad, Reza Nedaeinia, Rasoul Salehi, Leila Khani, Gordon A Ferns, Mir Hadi Jazayeri
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Abstract

Background: Previous studies have shown that CD134 (OX40) co-stimulation is involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) models and the antigen is expressed within multiple sclerosis lesions in humans. OX40 (CD134) is thought to be a secondary co-stimulatory immune checkpoint molecule that is expressed by T cells. This study aimed to evaluate the mRNA expression of OX40 and its serum levels in the peripheral blood of patients with Multiple Sclerosis (MS) or Neuromyelitis Optica (NMO).

Methods: Patients with MS (n = 60), NMO (n = 20), and 20 healthy subjects were recruited from Sina Hospital, Tehran, Iran. The diagnoses were confirmed by a specialist in clinical neurology. Peripheral venous blood was obtained from all subjects, and mRNA quantification of OX40 was conducted using real-time PCR. Serum samples were also obtained and the concentration of OX40 was determined using an enzyme-linked immunosorbent assay (ELISA).

Results: There was a significant correlation between the mRNA expression and serum levels of OX40 and disability as assessed using the expanded disability status scale (EDSS) in the patients with MS, but not in the patients with NMO. Expression of OX40 mRNA was significantly higher in the peripheral blood of MS patients compared to healthy individuals and NMO patients (*P < 0.05). In addition, serum OX40 concentrations were also significantly higher in patients with MS patients compared with healthy subjects (9.08 ± 2.48 vs. 1.49 ± 0.54 ng/ml; P = 0.041).

Conclusions: It appears that an increased expression of OX40 may be associated with the hyperactivation of T cells in patients with MS, and this may play a role in the pathogenesis of the disease.

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OX40在多发性硬化症与视神经脊髓炎患者中的表达比较及其诊断价值。
背景:已有研究表明,CD134 (OX40)共刺激参与实验性自身免疫性脑脊髓炎(EAE)模型的发病机制,且该抗原在人类多发性硬化症病变中表达。OX40 (CD134)被认为是由T细胞表达的次级共刺激免疫检查点分子。本研究旨在评估OX40 mRNA在多发性硬化症(MS)或视神经脊髓炎(NMO)患者外周血中的表达及其血清水平。方法:从伊朗德黑兰新浪医院招募多发性硬化症患者(60例)、NMO患者(20例)和健康者20例。临床神经病学专家证实了这些诊断。采集所有受试者外周静脉血,采用实时荧光定量PCR法定量OX40 mRNA。同时采集血清样本,采用酶联免疫吸附试验(ELISA)测定OX40的浓度。结果:用扩展残疾状态量表(EDSS)评估MS患者的mRNA表达和血清OX40水平与残疾之间存在显著相关性,而NMO患者则无显著相关性。MS患者外周血中OX40 mRNA的表达明显高于健康人及NMO患者(*P)。结论:OX40的表达升高可能与MS患者T细胞的过度活化有关,这可能在MS的发病机制中发挥作用。
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