Increased inflammation in the cerebral meninges is associated with extensive subpial cortical grey matter pathology in the forebrain and a more severe disease course in a substantial proportion of secondary progressive multiple sclerosis (SPMS) cases. It is not known whether this relationship extends to spinal cord pathology. We assessed the contribution of meningeal and parenchymal immune infiltrates to spinal cord pathology in SPMS cases characterized in the presence (F+) or absence (F−) of lymphoid‐like structures in the forebrain meninges. Transverse cryosections of cervical, thoracic and lumbar cord of 22 SPMS and five control cases were analyzed for CD20+ B cells, CD4+ and CD8+ T cells, microglia/macrophages (IBA‐1+), demyelination (myelin oligodendrocyte glycoprotein+) and axon density (neurofilament‐H+). Lymphoid‐like structures containing follicular dendritic cell networks and dividing B cells were seen in the spinal meninges of 3 out of 11 F+ SPMS cases. CD4+ and CD20+ cell counts were increased in F+ SPMS compared to F− SPMS and controls, whilst axon loss was greatest in motor and sensory tracts of the F+ SPMS cases (P  < 0.01). The density of CD20+ B cells of the spinal leptomeninges correlated with CD4+ T cells and total B and T cells of the meninges; with the density of white matter perivascular CD20+ and CD4+ lymphocytes (P  < 0.05); with white matter lesion area (P  < 0.05); and the extent of axon loss (P  < 0.05) in F+ SPMS cases only. We show that the presence of lymphoid‐like structures in the forebrain is associated with a profound spinal cord pathology and local B cell rich meningeal inflammation associates with the extent of cord pathology. Our work supports a principal role for B cells in sustaining inflammation and tissue injury throughout the CNS in the progressive disease stage.

中文翻译：

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富含 B 细胞的脑膜炎症与多发性硬化症中脊髓病理的增加有关。

脑膜炎症的增加与前脑中广泛的软膜下皮质灰质病理学相关，并且在相当大比例的继发性进行性多发性硬化症（SPMS）病例中，病程更严重。目前尚不清楚这种关系是否延伸到脊髓病理学。我们评估了前脑脑膜中存在（F+）或不存在（F-）淋巴样结构的 SPMS 病例中脑膜和实质免疫浸润对脊髓病理学的影响。对 22 例 SPMS 和 5 例对照病例的颈椎、胸椎和腰椎横向冷冻切片进行了 CD20+ B 细胞、CD4+ 和 CD8+ T 细胞、小胶质细胞/巨噬细胞 (IBA-1+)、脱髓鞘（髓磷脂少突胶质细胞糖蛋白+）和轴突密度（神经丝）的分析。 ‐H+)。11 例 F+ SPMS 病例中有 3 例的脊髓膜中发现含有滤泡树突状细胞网络和分裂 B 细胞的淋巴样结构。与 F− SPMS 和对照相比，F+ SPMS 中的 CD4+ 和 CD20+ 细胞计数增加，而 F+ SPMS 病例的运动和感觉束中轴突损失最大（P  < 0.01）。脊髓软脑膜的 CD20+ B 细胞密度与脑膜的 CD4+ T 细胞以及总 B 和 T 细胞相关；与血管周围白质CD20+、CD4+淋巴细胞密度比较( P  < 0.05); 与白质病变面积（P  < 0.05）；以及仅在 F+ SPMS 病例中轴突损失的程度 ( P  < 0.05)。我们发现，前脑中淋巴样结构的存在与严重的脊髓病理相关，而局部富含 B 细胞的脑膜炎症与脊髓病理的程度相关。我们的工作支持 B 细胞在疾病进展阶段维持整个中枢神经系统炎症和组织损伤中的主要作用。