Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8⁺/perforin⁺/granzyme A/B⁺ cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions.

Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies.

抗胶质纤维酸性蛋白（GFAP）脑膜脑脊髓炎（自身免疫性 GFAP 星形细胞病）是一种新的自身免疫性中枢神经系统（CNS）疾病，可通过脑脊液中存在抗 GFAP 自身抗体来诊断，大多数患者表现为脑膜脑脊髓炎。目前只有很少的神经病理学报告，并且对其致病机制知之甚少。我们对具有抗 GFAP 自身抗体的患者进行了两次尸检和九次 CNS 活检的组织病理学研究，发现主要是淋巴细胞，在一个尸检病例中发现了肉芽肿性炎症表型。炎症浸润由 B 细胞和 T 细胞组成，包括组织驻留记忆 T 细胞。尽管 GFAP 染色中没有明显的星形胶质细胞损伤，但我们发现细胞毒性 T 细胞介导的反应反映在 CD8 ⁺ /穿孔素⁺ /颗粒酶 A/B ⁺细胞的存在上，极化为星形胶质细胞。所有活检和两次尸检的反应性星形胶质细胞中 MHC-I 均上调，但在健康对照中并未上调。重要的是，我们观察到星形胶质细胞与补体因子 C4d 具有显着的免疫反应性。最后，我们在哈巴狗脑炎的尸检中深入了解了 GFAP 自身免疫的早期阶段，其特征是明显的脑膜脑炎，伴有选择性星形细胞损伤，病变中 GFAP 和 AQP4 缺失。

我们的组织病理学发现表明 GFAP 自身免疫中存在细胞毒性 T 细胞介导的免疫反应。星形胶质细胞上的补体 C4d 沉积可能代表星形胶质细胞反应性的原因或结果。在犬尸检病例中，选择性星形胶质细胞损伤在 GFAP 自身免疫的早期阶段很突出，但在人类疾病的亚急性和慢性阶段则轻微或不存在，这可能是由于星形胶质细胞的高再生潜力所致。淋巴细胞和肉芽肿表型可能反映病变发展的不同阶段或患者特异性免疫反应的改变。未来的研究将有必要调查病理亚型对临床病程和治疗策略的可能影响。