From the Department of Neuroimmunology (N.L.F., M.C.J.V. J.H., I.H., J.S.), Netherlands Institute for Neuroscience, Amsterdam, The Netherlands; Department of Neurology and MS Center, Amsterdam, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit (B.A.J.), The Netherlands; Institute for Neuropathology (K.H., T.K.), University Hospital Münster, Münster, Germany; Department of Experimental Immunology (J.H.), Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands; Swammerdam Institute for Life Sciences, University of Amsterdam (I.H.), The Netherlands; and MS Center ErasMS (J.S.), Departments of Neurology and Immunology, Erasmus Medical Center, Rotterdam, The Netherlands.
Neurol Neuroimmunol Neuroinflamm. 2021 Jan 27;8(2). doi: 10.1212/NXI.0000000000000955. Print 2021 Mar 4.
To determine whether B-cell presence in brainstem and white matter (WM) lesions is associated with poorer pathological and clinical characteristics in advanced MS autopsy cases.
Autopsy tissue of 140 MS and 24 control cases and biopsy tissue of 24 patients with MS were examined for CD20 B cells and CD138 plasma cells. The presence of these cells was compared with pathological and clinical characteristics. In corresponding CSF and plasma, immunoglobulin (Ig) G ratio and oligoclonal band (OCB) patterns were determined. In a clinical cohort of 73 patients, the presence of OCBs was determined during follow-up and compared to status at diagnosis.
In 34% of active and 71% of mixed active/inactive lesions, B cells were absent, which correlated with less pronounced meningeal B-cell infiltration ( < 0.0001). The absence of B cells and plasma cells in brainstem and WM lesions was associated with a longer disease duration ( = 0.001), less frequent secondary progressive MS compared with relapsing and primary progressive MS ( < 0.0001 and = 0.046, respectively), a lower proportion of mixed active/inactive lesions ( = 0.01), and less often perivascular T-cell clustering ( < 0.0001). Moreover, a lower CSF IgG ratio ( = 0.006) and more frequent absence of OCBs ( < 0.0001) were noted. In a clinical cohort, numbers of patients without OCBs in CSF were increased at follow-up (27.4%).
The absence of B cells is associated with a favorable clinical and pathological profile. This finding may reflect extremes of a continuum of genetic or environmental constitution, but also a regression of WM humoral immunopathology in the natural course of advanced MS.
确定 B 细胞在脑干和白质（WM）病变中的存在是否与高级多发性硬化症（MS）尸检病例的较差病理和临床特征有关。
对 140 例 MS 和 24 例对照病例的尸检组织以及 24 例 MS 患者的活检组织进行 CD20 B 细胞和 CD138 浆细胞检查。比较这些细胞的存在与病理和临床特征。在相应的脑脊液和血浆中，测定免疫球蛋白（Ig）G 比值和寡克隆带（OCB）模式。在 73 例临床队列患者中，在随访期间确定 OCB 的存在，并与诊断时的状态进行比较。
在 34%的活动性和 71%的混合活动性/非活动性病变中，B 细胞缺失，这与脑膜 B 细胞浸润程度较轻相关（<0.0001）。脑干和 WM 病变中 B 细胞和浆细胞的缺失与疾病持续时间较长（=0.001）、与复发型 MS 相比更少见继发性进展型 MS（<0.0001 和=0.046）、混合活动性/非活动性病变的比例较低（=0.01）以及血管周围 T 细胞聚集较少（<0.0001）相关。此外，还观察到脑脊液 IgG 比值较低（=0.006）和 OCB 缺失更为频繁（<0.0001）。在临床队列中，在随访时没有 CSF 中 OCB 的患者数量增加（27.4%）。
B 细胞的缺失与良好的临床和病理特征相关。这一发现可能反映了遗传或环境构成的连续体的极端情况，但也反映了 WM 体液免疫病理学在高级 MS 的自然病程中的消退。
