Department of Neurology, Translational Neuroimmunology Research Center (TNRC), Ann Romney Center for Neurologic Diseases (ARCND), Brigham and Women's Hospital, 60 Fenwood Road, 9002K, Boston, MA, 02115, USA.
Harvard Medical School, Boston, MA, 02115, USA.
J Neuroinflammation. 2023 May 30;20(1):131. doi: 10.1186/s12974-023-02811-z.
Multiple sclerosis (MS) is a disabling autoimmune demyelinating disorder affecting young people and causing significant disability. In the last decade, different microRNA (miRNA) expression patterns have been associated to several treatment response therapies such as interferon and glatiramer acetate. Nowadays, there is increasing interest in the potential role of miRNA as treatment response biomarkers to the most recent oral and intravenous treatments. In this study, we aimed to evaluate serum miRNAs as biomarkers of No Evidence of Disease Activity (NEDA-3) at 2 years in patients with relapsing remitting MS (RRMS) treated with fingolimod.
A Discovery cohort of 31 RRMS patients treated with fingolimod were identified from the CLIMB study and classified as No Evidence of Disease Activity (NEDA-3) or Evidence of Disease Activity (EDA-3) after 2 years on treatment. Levels of miRNA expression were measured at 6 months using human serum miRNA panels and compared in EDA-3 and NEDA-3 groups using the Wilcoxon rank sum test. A set of differentially expressed miRNA was further validated in an independent cohort of 22 fingolimod-treated patients. We found that 548a-3p serum levels were higher levels in fingolimod-treated patients classified as NEDA-3, compared to the EDA-3 group in both the Discovery (n = 31; p = 0.04) and Validation (n = 22; p = 0.03) cohorts 6 months after treatment initiation; miR-548a-3p provided an AUC of 0.882 discriminating patients with NEDA-3 at 2 years in the Validation cohort.
Our results show differences in miR-548a-3p expression at 6 months after fingolimod start in patients with MS with NEDA-3 at 2 years. These results provide class III evidence of the use of miR-548a-3p as biomarker of NEDA-3 in patients with fingolimod.
多发性硬化症（MS）是一种使人衰弱的自身免疫性脱髓鞘疾病，影响年轻人并导致严重残疾。在过去的十年中，不同的 microRNA（miRNA）表达模式与几种治疗反应疗法相关，如干扰素和格拉替雷。如今，人们越来越关注 miRNA 作为最新口服和静脉治疗反应生物标志物的潜在作用。在这项研究中，我们旨在评估接受芬戈莫德治疗的复发缓解型多发性硬化症（RRMS）患者 2 年内血清 miRNA 作为无疾病活动证据（NEDA-3）的生物标志物。
从 CLIMB 研究中确定了 31 名接受芬戈莫德治疗的 RRMS 患者的发现队列，并在治疗 2 年后将其分类为无疾病活动证据（NEDA-3）或有疾病活动证据（EDA-3）。使用人类血清 miRNA 面板在 6 个月时测量 miRNA 表达水平，并使用 Wilcoxon 秩和检验比较 EDA-3 和 NEDA-3 组。在另一组 22 名接受芬戈莫德治疗的患者中进一步验证了一组差异表达的 miRNA。我们发现，与 EDA-3 组相比，在治疗开始后 6 个月，被分类为 NEDA-3 的接受芬戈莫德治疗的患者中，548a-3p 血清水平更高，在发现队列中（n=31；p=0.04）和验证队列中（n=22；p=0.03）；miR-548a-3p 在验证队列中 2 年时区分 NEDA-3 患者的 AUC 为 0.882。
我们的结果表明，在接受芬戈莫德治疗的 MS 患者中，在 2 年内达到 NEDA-3 的患者中，在开始使用芬戈莫德后 6 个月时，miR-548a-3p 的表达存在差异。这些结果提供了 III 级证据，证明 miR-548a-3p 可作为接受芬戈莫德治疗的患者 NEDA-3 的生物标志物。
