case_images: PMC10470460_01
case_images: Imaging and profile of cytotoxic T- and B- subsets from a patient with AQP4-positive NMOSD. MR images of the cervical and thoracic spine demonstrate spinal cord involvement. (A) A sagittal contrast-enhanced T1-weighted image of the cervical spine shows a focal enhancing lesion at the C2-3 level (curved arrow). (B) The sagittal T2-weighted image shows diffuse thoracolumbar spinal cord atrophy and some multiple short segments of hyperintensity (arrowhead) along the spinal cord. This pattern may be present in chronic phases, and lesions tend to fragment into shorter segments after high-dose steroids or during remission. (C) The axial T2-weighted image shows a bright spotty lesion located centrally at the T2 level (arrow) and also demonstrates spine cord atrophy. (D) Flow cytometry analyses show percentages of CD8+GzmB+ (39.6%) and CD4+GzmB+ (63.6%) T lymphocytes beyond CD19+GzmB+ B cells (54.0%) identified in the peripheral blood.
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case_images: PMC10470460_01_fneur-14-1208977-g0001.jpg
case_images: F1
case_images: Cervical spine MRI showed a focal enhancing lesion at the C2-3 level and spinal cord atrophy (Figures 1A-C).
case_images: Clinical history and hypothesis on the involvement of cytotoxic T- and B- subsets during AQP4-positive NMOSD physiopathology. (A) Main findings of the clinical history until deep vein thrombosis (DVT)/pulmonary thromboembolism (PTE) outcome. (B) Th17 subsets (expressing IL-17), innate cells, and complement system may promote peripheral inflammation, eventually disrupting the blood-brain barrier (BBB) during AQP4-positive NMOSD pathogenesis. Considering well-established pathophysiological mechanisms during disease, approved monoclonal antibodies used to treat NMOSD are shown. We hypothesize that cytotoxic (CD8+ and CD4+) T- and B- subsets may also support BBB damage by expressing and releasing serine-protease granzyme-B (GzmB). Thus, once AQP4-IgG antibodies enter the central nervous system (CNS), they bind with astrocyte end-feet characterizing a primarily astrocytopathy. Deposition of complement factors is also observed (C1q, among other factors) and terminally leads to the formation of membrane attack complex (MAC). Reactive astrocytes can release pro-inflammatory cytokines (e.g., IL-1, IL-6, TNF-alpha) upon stimulation. Eosinophils, neutrophils, and other innate cells (e.g., macrophages, not shown) are also implicated in the oligodendrocyte and neuronal loss secondarily to the astrocytopathy. Created with Biorender.com.
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case_images: F2
case_images: In March/2019, the patient died due to pulmonary thromboembolism (PTE) and lower extremity deep vein thrombosis (DVT) (clinical history is summarized in Figure 2A).