多灶性运动神经病变患者体液IgM抗gm1自身免疫反应自发调节的证据

IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Journal of the Peripheral Nervous System Pub Date : 2023-07-27 DOI:10.1111/jns.12583
Marianna Di Egidio, Cristian R. Bacaglio, Rocio Arrejoría, Andrés M. Villa, Gustavo A. Nores, Pablo H. H. Lopez
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引用次数: 0

摘要

背景和目的多灶性运动神经病(MMN)是一种以缓慢进行性远端不对称无力为特征的周围神经疾病,伴有轻微或无感觉损伤。目前,大量证据支持IgM抗gm1抗体在疾病发病机制中的直接致病作用。MMN血清中gm1特异性IgM抗体阳性的患者比没有这些抗体的患者有更多的虚弱、残疾和轴突损失。在一组神经病变患者中筛选IgM抗gm1抗体时,我们注意到在一些MMN患者中IgM抗gm1天然自身反应性缺失或显著降低,提示自身反应性的自我控制机制。我们的目的是了解MMN患者缺乏对GM1的天然反应性。方法采用高效薄层色谱-免疫染色法、可溶性结合抑制法、Protein-G或gm1亲和柱法和点印迹法,分析游离IgM抗gm1或其复合物对阻断IgG的反应性。结果我们在MMN患者中发现了IgG免疫球蛋白介导的IgM抗gm1抗体的免疫调节,其特点是:(i)由于免疫调节IgG依赖机制而缺乏天然的IgM抗gm1自身反应性;(ii)血清中存在天然的和与疾病相关的IgM抗gm1 /IgG阻断Ab复合物;(iii)对天然IgM抗gm1抗体(Abs)的高水平IgG阻断。解释我们的观察揭示了针对IgM抗gm1抗体的自发IgG依赖的免疫调节机制,该机制可以部分解释通常缓慢进展的临床过程的波动,这是该疾病的特征。允许在血清阴性患者中识别针对GM1神经节苷脂的自身免疫反应。
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Evidence for spontaneous regulation of the humoral IgM anti-GM1 autoimmune response by IgG antibodies in multifocal motor neuropathy patients

Background and Aims

Multifocal motor neuropathy (MMN) is a peripheral nerve disorder characterized by slow progressive distal asymmetric weakness with minimal or no sensory impairment. Currently, a vast evidence supports a direct pathogenic role of IgM anti-GM1 antibodies on disease pathogenesis. Patients with MMN seropositive for GM1-specific IgM antibodies have significantly more weakness, disability and axon loss than patients without these antibodies. During the screening for IgM anti-GM1 antibodies in a cohort of patients with neuropathy we noticed an absence or significant reduction of natural IgM anti-GM1 autoreactivity in some patients with MMN, suggesting a mechanism of self-control of autoreactivity. We aim to understand the lack of natural reactivity against GM1 in MMN patients.

Methods

The presence of free IgM anti-GM1 reactivity or its complex to blocking IgG was analysed by combining high performance thin layer chromatography-immunostaining, soluble binding inhibition assays, Protein-G or GM1-affinity columns and dot blot assays.

Results

We identified in MMN patients an immunoregulation of IgM anti-GM1 antibodies mediated by IgG immunoglobulins characterized by: (i) lack of natural IgM anti-GM1 autoreactivity as a result of a immunoregulatory IgG-dependent mechanism; (ii) presence of natural and disease-associated IgM anti-GM1/IgG blocking Ab complexes in sera; and (iii) high levels of IgG blocking against natural IgM anti-GM1 antibodies (Abs.

Interpretation

Our observations unmask a spontaneous IgG-dependent mechanism of immunoregulation against IgM anti-GM1 antibodies that could explain, in part, fluctuations in the usually slowly progressive clinical course that characterizes the disease and, at the same time, allows the identification of an autoimmune response against GM1 ganglioside in seronegative patients.

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来源期刊
CiteScore
6.10
自引率
7.90%
发文量
45
审稿时长
>12 weeks
期刊介绍: The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.
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