Multiple Sclerosis Center, Sheba Medical Center, Ramat-Gan, Israel.
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
Ann Clin Transl Neurol. 2021 Jan;8(1):81-94. doi: 10.1002/acn3.51244. Epub 2020 Nov 16.
To determine whether pediatric-onset multiple sclerosis (POMS) and adults-onset multiple sclerosis (AOMS) patients are different in initial disease severity and recovery and to investigate the associations with peripheral blood mononuclear cells (PBMCs) transcriptional profiles.
Clinical and radiological severity of first and second relapses and 6-month recovery were analyzed in 2153 multiple sclerosis (MS) patients and compared between POMS (onset at 8-18years old) and AOMS (onset at 19-40 years old) patients. PBMCs transcriptomes of 15 POMS and 15 gender-matched AOMS patients were analyzed 6 months after the first relapse and compared to 55 age-matched healthy controls. Differentially Expressed Genes (DEGs) with a false discovery rate ≤ 10% were evaluated using the Partek software.
POMS had increased Expanded Disability Status Scale (EDSS) score at first and second relapses, higher brain gadolinium-enhancing T1-lesions volume at first relapse, and more complete recovery after both relapses compared to AOMS. POMS patients, who recovered completely from the first relapse, were characterized by 19 DEGs that were mainly related to suppression of antigen presentation. Six upstream regulators of these genes were differentially expressed between pediatric and adult healthy controls. POMS patients, who showed no recovery from the first relapse, were characterized by 28 DEGs that were mainly associated with B-cell activation. Five upstream regulators of these genes were differentially expressed between pediatric and adult healthy controls.
POMS patients may have more severe first and second relapses than AOMS. However, most often, POMS have better recovery that may be attributed to PBMCs age-related transcriptional profiles associated with antigen presentation and B-cell activation.
确定儿童发病多发性硬化症（POMS）和成人发病多发性硬化症（AOMS）患者在初始疾病严重程度和恢复方面是否存在差异，并探讨其与外周血单核细胞（PBMC）转录谱的关系。
分析了 2153 例多发性硬化症（MS）患者的首次和第二次复发的临床和放射学严重程度以及 6 个月的恢复情况，并将 POMS（发病年龄 8-18 岁）和 AOMS（发病年龄 19-40 岁）患者进行了比较。分析了 15 例 POMS 和 15 例性别匹配的 AOMS 患者在首次复发后 6 个月的 PBMC 转录组，并与 55 名年龄匹配的健康对照进行了比较。使用 Partek 软件评估了假发现率≤10%的差异表达基因（DEG）。
与 AOMS 相比，POMS 患者在首次和第二次复发时的扩展残疾状况量表（EDSS）评分更高，首次复发时的脑钆增强 T1 病变体积更大，两次复发后的恢复更完全。首次复发完全恢复的 POMS 患者的特征是 19 个 DEG，这些基因主要与抗原呈递的抑制有关。这些基因的 6 个上游调节剂在儿科和成人健康对照组之间表达不同。首次复发无恢复的 POMS 患者的特征是 28 个 DEG，这些基因主要与 B 细胞激活有关。这些基因的 5 个上游调节剂在儿科和成人健康对照组之间表达不同。
与 AOMS 相比，POMS 患者的首次和第二次复发可能更严重。然而，大多数 POMS 患者的恢复情况更好，这可能归因于 PBMC 与抗原呈递和 B 细胞激活相关的年龄相关转录谱。
