A role for pathogenic autoantibodies in small fiber neuropathy?
A role for pathogenic autoantibodies in small fiber neuropathy?
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DOI：
10.3389/fnmol.2023.1254854
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发表时间：
2023
影响因子：
4.8
通讯作者：
Dawes, John M.
中科院分区：
文献类型：
--
作者：
Daifallah, Omar;Farah, Adham;Dawes, John M.
关键词：
免疫系统在神经性疼痛中起作用，包括自身免疫机制（如自身抗体）。临床研究已经确定了一些神经性疼痛常见的情况，这些情况与神经系统内靶向抗原的自身抗体有关。有趣的是，感觉症状可以通过免疫疗法或血浆交换得到缓解，这表明这些患者的疼痛是抗体介导的。最近的临床前研究直接解决了这个问题。例如，患者CASPR2自身抗体的被动转移导致小鼠疼痛敏感性增加和感觉神经元兴奋性增强，证实了致病性，并证明患者自身抗体是引起神经性疼痛的一种机制。小纤维神经病（SFN）仅影响小感觉纤维（通常是伤害感受器），其特征是严重的神经性疼痛。已知的病因包括糖尿病、B12缺乏症和罕见的钠通道基因变异，尽管约50%的病例是特发性的。SFN与自身免疫性疾病（如Sjorgen综合征、结节病和乳糜泻）有关，静脉注射免疫球蛋白（IVIG）已被证明是一种有效的治疗方法。已经鉴定出自身抗体，在某些情况下，SFN患者IgG在小鼠中的被动转移可以重现神经性疼痛样行为。在这里，我们将讨论与病原性自身抗体导致SNF相关的临床和临床前数据。我们讨论假定的致病抗体，细胞靶点和分子机制，通过它们引起感觉神经元损伤和神经性疼痛的发展。最后，我们将对未来的方向进行评论，这可能会进一步深入了解患者SFN的机制。
The immune system has a role in neuropathic pain which includes autoimmune mechanisms (e.g., autoantibodies). Clinical studies have identified a number of conditions where neuropathic pain is common and that are associated with autoantibodies targeting antigens within the nervous system. Interestingly sensory symptoms can be relieved with immunotherapies or plasma exchange, suggesting that pain in these patients is antibody-mediated. Recent preclinical studies have directly addressed this. For example, passive transfer of CASPR2 autoantibodies from patients cause increased pain sensitivity and enhanced sensory neuron excitability in mice confirming pathogenicity and demonstrating that patient autoantibodies are a mechanism to cause neuropathic pain. Small fiber neuropathy (SFN) exclusively affects small sensory fibers (typically nociceptors) and is characterized by severe neuropathic pain. Known causes include diabetes, B12 deficiency and rare variants in sodium channel genes, although around 50% of cases are idiopathic. SFN is associated with autoimmune conditions such as Sjorgen’s syndrome, Sarcoidosis and Celiac disease and immunotherapy in the form of Intravenous immunoglobulin (IVIG) has proved an effective treatment. Autoantibodies have been identified and, in some cases, passive transfer of SFN patient IgG in mice can recapitulate neuropathic pain-like behavior. Here we will discuss clinical and preclinical data relating to the idea that pathogenic autoantibodies contribute to SNF. We discuss putative pathogenic antibodies, cellular targets and the molecular mechanisms by which they cause sensory neuron damage and the development of neuropathic pain. Finally, we will comment on future directions which may provide further insights into the mechanisms underlying SFN in patients.
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影响因子：
16.2
作者：
Dawes JM;Weir GA;Middleton SJ;Patel R;Chisholm KI;Pettingill P;Peck LJ;Sheridan J;Shakir A;Jacobson L;Gutierrez-Mecinas M;Galino J;Walcher J;Kühnemund J;Kuehn H;Sanna MD;Lang B;Clark AJ;Themistocleous AC;Iwagaki N;West SJ;Werynska K;Carroll L;Trendafilova T;Menassa DA;Giannoccaro MP;Coutinho E;Cervellini I;Tewari D;Buckley C;Leite MI;Wildner H;Zeilhofer HU;Peles E;Todd AJ;McMahon SB;Dickenson AH;Lewin GR;Vincent A;Bennett DL
通讯作者：
Bennett DL
影响因子：
2.8
作者：
Bayraktutar, Betul N.;Atocha, Vanessa;Hamrah, Pedram
通讯作者：
Hamrah, Pedram
影响因子：
81.5
作者：
Colloca, Luana;Ludman, Taylor;Raja, Srinivasa N.
通讯作者：
Raja, Srinivasa N.
影响因子：
4.8
作者：
Lussier, MP;Cayouette, S;Boulay, G
通讯作者：
Boulay, G
影响因子：
16.6
作者：
Burk K;Mire E;Bellon A;Hocine M;Guillot J;Moraes F;Yoshida Y;Simons M;Chauvet S;Mann F
通讯作者：
Mann F