Translational Neuroimmunology Research Center (TNRC), Ann Romney Center for Neurologic Diseases (ARCND), Department of Neurology, Brigham and Women's Hospital, 60 Fenwood Road, 9002K, Boston, MA, 02115, USA.
Brigham MS Center, Department of Neurology, Brigham and Women's Hospital, Boston, MA, 02115, USA.
J Neuroinflammation. 2023 Jun 1;20(1):136. doi: 10.1186/s12974-023-02816-8.
Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder which may cause long-term disability. MicroRNA (miRNA) are stable, non-coding molecules that have been identified in our Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB)-cohort, as well as other international cohorts, as potential disease biomarkers in MS. However, few studies have evaluated the association of miRNA expression early in the MS disease course with long-term outcomes. Therefore, we aimed to evaluate the potential role of three candidate serum miRNAs previously correlated with MS disability in patients with MS, miR-320b, miR-25-3p and miRNA 486-5p, as early biomarkers of MS disability at 10-year follow-up.
We included 144 patients with serum obtained within three years of MS onset. miRNA expression was measured by RNA extraction followed by RT-PCR. Demographic, clinical, brain MRI and other biomarkers were collected. The primary outcome was the association between early miRNA expression and retaining benign MS, defined as EDSS ≤ 2 at 10-year follow-up. Among the 144 patients, 104 were benign and 40 were not benign at 10-year follow-up. 89 (62%) were women, with mean age at onset 37.7 (SD: 9.6) years. Patients who retained benign MS had lower values of miR-25-3p (p = 0.047) and higher miR-320b (p = 0.025) values. Development of SPMS was associated with higher miR-320b (p = 0.002) levels. Brain parenchymal fraction at year 10 was negatively correlated with miR-25-3p (p = 0.0004) and positively correlated with miR-320b (p = 0.006). No association was found between miR-486-5p and any outcome, and 10-year T2-lesion volume was not associated with any miRNA.
Our results show that miR-320b and miR-25-3p expression are early biomarkers associated with MS severity and brain atrophy. This study provides class III evidence of that miR-320b and miR-25-3p are associated with long-term MS disability which may be a potential tool to risk-stratify patients with MS for early treatment decisions.
多发性硬化症（MS）是一种慢性脱髓鞘自身免疫性疾病，可能导致长期残疾。微小 RNA（miRNA）是稳定的非编码分子，在布里格姆妇女医院（Brigham and Women's Hospital，BWH）的多发性硬化症综合纵向研究（Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital，CLIMB）队列以及其他国际队列中被确定为 MS 的潜在疾病生物标志物。然而，很少有研究评估 MS 病程早期 miRNA 表达与长期结局的相关性。因此，我们旨在评估三种候选血清 miRNA（miR-320b、miR-25-3p 和 miRNA 486-5p）在 MS 患者中的表达，这些 miRNA 先前与 MS 残疾相关，作为 10 年随访时 MS 残疾的早期生物标志物。
我们纳入了 144 例 MS 发病三年内获得血清的患者。通过 RNA 提取和 RT-PCR 测量 miRNA 表达。收集人口统计学、临床、脑 MRI 和其他生物标志物。主要结局是早期 miRNA 表达与保留良性 MS 的相关性，定义为 10 年随访时 EDSS≤2。在 144 例患者中，104 例为良性，40 例为非良性。10 年随访时，89 例（62%）为女性，发病年龄平均为 37.7（标准差：9.6）岁。保留良性 MS 的患者 miR-25-3p 值较低（p=0.047），miR-320b 值较高（p=0.025）。进展为继发进展型多发性硬化症（SPMS）与 miR-320b 水平升高有关（p=0.002）。第 10 年脑实质分数与 miR-25-3p 呈负相关（p=0.0004），与 miR-320b 呈正相关（p=0.006）。miR-486-5p 与任何结局均无关联，10 年 T2 病变体积与任何 miRNA 均无关联。
我们的结果表明，miR-320b 和 miR-25-3p 的表达是与 MS 严重程度和脑萎缩相关的早期生物标志物。本研究提供了 III 级证据表明 miR-320b 和 miR-25-3p 与长期 MS 残疾相关，这可能是一种潜在的工具，用于对 MS 患者进行风险分层，以做出早期治疗决策。
