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Unraveling B lymphocytes in CNS inflammatory diseases: Distinct mechanisms and treatment targets.
解开CNS炎症性疾病中的B淋巴细胞: 不同的机制和治疗靶点。
- 影响因子:25.02
- DOI:10.1212/WNL.0000000000010789
- 作者列表:"Klein da Costa B","Brant de Souza Melo R","Passos GRD","Gomes Meneses Sevilha Castro D","Becker J","Bar-Or A","Sato DK
- 发表时间:2020-10-20
Abstract
:Specific therapies targeting B lymphocytes in multiple sclerosis (MS) have demonstrated reductions in disease activity and disability progression. Several observational studies have also shown the effects of targeting B lymphocytes in other rare CNS inflammatory diseases, such as neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis (AE). However, some drugs targeting cytokine receptors involved in B-lymphocyte maturation and proliferation resulted in negative outcomes in MS. These apparently conflicting findings have stimulated research on the pathophysiologic mechanisms of B lymphocytes in CNS inflammatory diseases. It has been demonstrated that B lymphocytes participate in the pathogenesis of these conditions as antigen-presenting cells, producing proinflammatory cytokines that induce Th1 and Th17 responses and producing antibodies. However, they are also able to produce anti-inflammatory cytokines, such as interleukin-10, functioning as regulators of autoimmunity. Understanding these diverse effects is essential for the development of focused treatments. In this review, we discuss the possible mechanisms that underlie B-lymphocyte involvement in MS, NMOSD, and AE and the outcomes obtained by treatments targeting B lymphocytes.
摘要
: 针对多发性硬化症 (MS) 中的B淋巴细胞的特异性疗法已证明疾病活动和残疾进展的减少。一些观察性研究也显示了靶向B淋巴细胞在其他罕见的CNS炎症性疾病中的作用,例如视神经脊髓炎谱系障碍 (NMOSD) 和自身免疫性脑炎 (AE)。然而,一些靶向参与B淋巴细胞成熟和增殖的细胞因子受体的药物导致了MS的负面结果。这些明显矛盾的发现刺激了对B淋巴细胞在CNS炎症性疾病中的病理生理机制的研究。已经证明,B淋巴细胞作为抗原呈递细胞参与这些病症的发病机制,产生诱导Th1和Th17应答的促炎细胞因子并产生抗体。然而,它们也能够产生抗炎细胞因子,如interleukin-10,作为自身免疫的调节剂。了解这些不同的效果对于重点治疗的发展至关重要。在这篇综述中,我们讨论了B淋巴细胞参与MS、NMOSD和AE的可能机制,以及通过靶向B淋巴细胞的治疗获得的结果。
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METHODS::Purpose: To report on ocular Vogt-Koyanagi-Harada (VKH)-like syndrome under vemurafenib treatment for metastatic melanoma.Design: A case report.Method: Description of clinical and imaging manifestations including fundus photography, fluorescein, and indocyanine green angiography.Results: A 46-year-old Thai female was diagnosed with metastatic melanoma of the skin and had been treated with multiple surgical excisions, radiotherapy, and vemurafenib (initial dose 480 mg orally twice daily, subsequently increased to maximum dose of 960 mg twice daily). After 6 months of vemurafenib use, she complained of bilateral redness and photophobia and was diagnosed with bilateral anterior uveitis, which was topically treated. Two weeks later, her visual acuity (VA) sharply deteriorated to 20/80 and counting fingers. Ocular examination at that stage stronly resembled acute VKH disease. She exhibited intraocular inflammation, and her fundus examination revealed bilateral optic disc swelling and serous retinal detachment. Fluorescein angiogram showed disc leakage and multiple pinpoint hyperfluorescence leakage spots and indocyanine green demonstrated multiple hypofluorescent spots. Oral prednisolone 30 mg/day was commenced while vemurafenib medication was ceased. Three weeks later, her vision improved, and serous retinal detachment subsided. However, her cutaneous melanoma recurred.Conclusions: Vemurafenib, a potential adjunct treatment for metastatic melanoma, was complicated by the development of panuveitis, papillitis, and multiple serous detachments. These ocular symptoms were similar to the presentation of acute VKH syndrome.
METHODS::Comprehensive reviews of the clinical characteristics and pathogenesis of Aicardi-Goutières syndrome (AGS), particularly its contextualization within a putative type I interferonopathy framework, already exist. However, recent reports of attempts at treatment suggest that an assessment of the field from a therapeutic perspective is warranted at this time. Here, we briefly summarize the neurological phenotypes associated with mutations in the seven genes so far associated with AGS, rehearse current knowledge of the pathology as it relates to possible treatment approaches, critically appraise the potential utility of therapies, and discuss the challenges in assessing clinical efficacy. WHAT THIS PAPER ADDS: Progress in understanding AGS disease pathogenesis has led to the first attempts at targeted treatment. Further rational therapies are expected to become available in the short- to medium-term.
METHODS::Purpose: To report the efficacy of adalimumab in a case of chronic Vogt-Koyanagi-Harada (VKH) disease refractory to conventional corticosteroids and immunosuppressive therapy and complicated by central serous chorioretinopathy (CSC).Case report: A 66-year-old woman diagnosed with VKH was treated with intravenous corticosteroids followed by oral corticosteroids and cyclosporine. However, systemic corticosteroids could not be tapered because of recurrent ocular inflammation and systemic complications (diabetes mellitus, moon face, bone weakness), while CSC appeared in both eyes. A diagnosis of chronic VKH resistant to medications complicated by corticosteroid-induced CSC was made. Systemic corticosteroids and cyclosporine were tapered and adalimumab initiated. Bilateral ocular inflammation and CSC were gradually reduced and visual acuity improved without any adverse effect. Twelve months after starting adalimumab monotherapy, no signs of active VKH and CSC were present.Conclusions: Adalimumab is one of the effective therapeutic options for refractory VKH disease complicated with corticosteroid-induced adverse effects.
神经系统自身免疫性疾病是以自身免疫细胞、免疫分子等攻击神经系统为主要致病机制的自身免疫性疾病。在免疫反应中,作用于神经系统自身抗原的致病抗体统称为神经系统自身抗体。