Departments of Neurology (C.C.H., B.C.H., S.T., M.A.M., F.J.Q., R.G., H.L.W, R.B.) and Department of Radiology (R.B.); Brigham and Women's Hospital (C.C.H., B.C.H., S.T., M.A.M., F.J.Q., R.G., H.L.W, R.B.); Laboratory for Neuroimaging Research (C.C.H., S.T., R.H.); Partners Multiple Sclerosis Center (C.C.H., B.C.H., S.T., M.A.M., F.J.Q., R.G., H.L.W, R.B.); Ann Romney Center for Neurologic Diseases (C.C.H., B.C.H., S.T., M.A.M., F.J.Q., R.G., H.L.W, R.B.); and Harvard Medical School (C.C.H., B.C.H., S.T., M.A.M., F.J.Q., R.G., H.L.W., R.B.), Boston, MA.
Neurol Neuroimmunol Neuroinflamm. 2019 Feb 14;6(2):e530. doi: 10.1212/NXI.0000000000000530. eCollection 2019 Mar.
To classify and immunologically characterize persons with MS based on brain lesions and atrophy and their associated microRNA profiles.
Cerebral T2-hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) were quantified and used to define MRI phenotypes as follows: type I: low T2LV, low atrophy; type II: high T2LV, low atrophy; type III: low T2LV, high atrophy; type IV: high T2LV, high atrophy, in a large cross-sectional cohort (n = 1,088) and a subset with 5-year lngitudinal follow-up (n = 153). Serum miRNAs were assessed on a third MS cohort with 2-year MRI phenotype stability (n = 98).
One-third of the patients had lesion-atrophy dissociation (types II or III) in both the cross-sectional and longitudinal cohorts. At 5 years, all phenotypes had progressive atrophy ( < 0.001), disproportionally in type II (BPF -2.28%). Only type IV worsened in physical disability. Types I and II showed a 5-year MRI phenotype conversion rate of 33% and 46%, whereas III and IV had >90% stability. Type II switched primarily to IV (91%); type I switched primarily to II (47%) or III (37%). Baseline higher age ( = 0.006) and lower BPF ( < 0.001) predicted 5-year phenotype conversion. Each MRI phenotype demonstrated an miRNA signature whose underlying biology implicates blood-brain barrier pathology: hsa.miR.22.3p, hsa.miR.361.5p, and hsa.miR.345.5p were the most valid differentiators of MRI phenotypes.
MRI-defined MS phenotypes show high conversion rates characterized by the continuation of either predominant neurodegeneration or inflammation and support the partial independence of these 2 measures. MicroRNA signatures of these phenotypes suggest a role for blood-brain barrier integrity.
根据脑损伤和萎缩以及相关 microRNA 谱对 MS 患者进行分类和免疫特征分析。
对脑 T2 高信号病变体积（T2LV）和脑实质分数（BPF）进行定量分析，并定义 MRI 表型如下：I 型：低 T2LV，低萎缩；II 型：高 T2LV，低萎缩；III 型：低 T2LV，高萎缩；IV 型：高 T2LV，高萎缩，在一个大型横断面队列（n=1088）和一个具有 5 年纵向随访的亚组（n=153）中进行。对第三个 MS 队列（n=98）的血清 microRNA 进行了评估，这些患者在 2 年内 MRI 表型稳定。
横断面和纵向队列中，三分之一的患者存在病变-萎缩分离（II 型或 III 型）。5 年后，所有表型均出现进行性萎缩（<0.001），尤以 II 型更为显著（BPF-2.28%）。仅 IV 型在身体残疾方面恶化。I 型和 II 型的 5 年 MRI 表型转换率分别为 33%和 46%，而 III 型和 IV 型的稳定性>90%。II 型主要向 IV 型转换（91%）；I 型主要向 II 型（47%）或 III 型（37%）转换。基线时年龄较高（=0.006）和 BPF 较低（<0.001）预测 5 年表型转换。每种 MRI 表型都有一个 microRNA 特征，其潜在生物学提示血脑屏障病理学：hsa.miR.22.3p、hsa.miR.361.5p 和 hsa.miR.345.5p 是最有效的 MRI 表型区分物。
MRI 定义的 MS 表型具有较高的转换率，其特征是要么继续主要的神经退行性变，要么继续炎症，这支持这两种措施的部分独立性。这些表型的 microRNA 特征提示血脑屏障完整性起作用。
