Department of Gastroenterology and Hepatology, AGEM Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
Acta Neuropathol Commun. 2023 Mar 25;11(1):51. doi: 10.1186/s40478-023-01538-5.
Although various neurodegenerative disorders have been associated with coeliac disease (CD), the underlying neuropathological link between these brain and gut diseases remains unclear. We postulated that the neuronal damage sporadically observed in CD patients is immune-mediated. Our aim was to determine if the loss of neurons, especially Purkinje cells, coincides with microglia activation and T- and B-cell infiltration in the cerebellum of patients with CD and a concomitant idiopathic neurological disease affecting the cerebellum (NeuroCD). Post-mortem cerebellar tissue was collected of validated NeuroCD cases. Gender- and age-matched genetic spinocerebellar ataxia (SCA) controls and non-neurological controls (NNC) were selected based on clinical reports and pathological findings. Cerebellar tissue of seventeen patients was included (6 NeuroCD, 5 SCA, 6 NNC). In SCA cases we found that the Purkinje cell layer was 58.6% reduced in comparison with NNC. In NeuroCD cases this reduction was even more prominent with a median reduction of 81.3% compared to NNC. Marked increased numbers of both CD3+ and CD8+ cells were observed in the NeuroCD but not in SCA patients. This coincided with significantly more microglial reactivity in NeuroCD patients. These findings demonstrate that the massive loss of Purkinje cells in the cerebellum of neuro CD patients is accompanied by local innate and T-cell mediated immune responses.
虽然各种神经退行性疾病都与乳糜泻(CD)有关,但这些大脑和肠道疾病之间的潜在神经病理学联系尚不清楚。我们假设,在 CD 患者中偶尔观察到的神经元损伤是免疫介导的。我们的目的是确定神经元的丧失,特别是浦肯野细胞,是否与小脑内小胶质细胞的激活以及 T 细胞和 B 细胞浸润相吻合,这些患者患有 CD 和同时影响小脑的特发性神经疾病(NeuroCD)。收集了经证实的 NeuroCD 病例的死后小脑组织。根据临床报告和病理发现,选择了性别和年龄匹配的遗传性脊髓小脑共济失调(SCA)对照和非神经对照(NNC)。纳入了十七名患者的小脑组织(6 名 NeuroCD,5 名 SCA,6 名 NNC)。在 SCA 病例中,我们发现与 NNC 相比,浦肯野细胞层减少了 58.6%。在 NeuroCD 病例中,与 NNC 相比,这种减少更为明显,中位数减少了 81.3%。在 NeuroCD 患者中观察到 CD3+和 CD8+细胞数量明显增加,但在 SCA 患者中则没有。这与 NeuroCD 患者中明显更多的小胶质细胞反应相一致。这些发现表明,NeuroCD 患者小脑浦肯野细胞的大量丧失伴随着局部先天和 T 细胞介导的免疫反应。