Clinical and Experimental Neuroimmunology最新文献

Age-associated B cells (ABCs), initially identified in aged mice, are a distinct B cell subset that plays crucial roles in autoimmune diseases through the production of autoantibodies, proinflammatory cytokines, and antigen presentation. Although a definitive set of markers for identifying ABCs has not yet been established, they are commonly characterized by the expression of CD11c, CD11b, and the transcription factor T-bet, along with reduced levels of CD21, either alone or in combination. ABC differentiation is driven by Toll-like receptor 7 (TLR7) signaling in conjunction with cytokines such as interleukin-21 (IL-21) and interferon-gamma (IFNγ). Importantly, ABCs expand in the blood or inflamed tissues and exhibit pathogenic functions in various autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, Crohn's disease, axial spondyloarthritis, Grave's disease, and multiple sclerosis. Recently, ABCs have been implicated in neuromyelitis optica spectrum disorder (NMOSD), a chronic inflammatory astrocytopathy mediated by anti-AQP4 antibody-producing B cells characterized by relapses and remissions. In the acute phase, CD21^lo B cells can differentiate into anti-AQP4 antibody-producing cells and expand in both cerebrospinal fluid and blood. In the chronic phase, an increased frequency of CD11c^hi B cells in the blood correlates with chronic neurological damage or brain injury. T peripheral helper type 1 cells, which produce IFNγ and IL-21, may support ABC differentiation in both phases. This review explores the role of ABCs in NMOSD, highlighting key studies that link ABC subsets to disease pathology. Understanding ABC-mediated mechanisms in NMOSD may open avenues for novel therapeutic strategies.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is an autoimmune inflammatory central nervous system disease. Recent neuropathological findings indicate that GFAP-specific cluster of differentiation (CD)8⁺ T cells are likely the effectors of GFAP-A. Of 387 individuals in Japan identified as having GFAP-A, most presented with headache and/or fever followed by neurological symptoms including consciousness disturbance, urinary dysfunction, hyperreflexia, movement disorders, and papilledema. Sixteen (5.9%) of the 270 GFAP-A patients tested had coexisting antibodies. Cerebrospinal fluid (CSF) examination revealed lymphocytic pleocytosis and increased protein levels. Moreover, transiently increased CSF adenosine deaminase, decreased glucose, and positive oligoclonal band results were sometimes observed. Brain magnetic resonance imaging (MRI) occasionally showed T2-hyperintensity lesions. Linear perivascular radial gadolinium-enhancement patterns were observed and may be an imaging hallmark of GFAP-A. Spinal cord MRI sometimes exhibited T2-hyperintensity spinal cord lesions, most of which were longitudinally extensive. Most patients were treated with immunotherapies, including intravenous methylprednisolone pulse therapy with or without intravenous immunoglobulin therapy and/or plasma exchange; this was followed by oral corticosteroid therapy, which was gradually tapered. Some refractory patients received second-line immunotherapies including rituximab or cyclophosphamide. In 203 patients with follow-up ≥ 6 months, the median modified Rankin scale score at last follow-up was 1 (range: 0–6); however, 44 patients (21.7%) had scores of 3 or greater, and six patients died. The most common neurological finding at last follow-up was cognitive dysfunction, followed by urinary dysfunction; the recurrence rate was 10.5%. CSF GFAP-immunoglobulin G should be examined in patients who present with these characteristic clinical and radiological features.

Trial Registration: Autoimmune GFAP astrocytopathy registry (UMIN: 000054387).