Department of Laboratory Medicine and Pathology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Ann Neurol. 2012 Mar;71(3):417-26. doi: 10.1002/ana.22674.
To test the hypothesis that autoimmunity induced by inhalation of aerosolized brain tissue caused outbreaks of sensory-predominant polyradiculoneuropathy among swine abattoir employees in the Midwestern United States.
Mice were exposed intranasally, 5 days per week, to liquefied brain tissue. Serum from exposed mice, patients, and unaffected abattoir employees were analyzed for clinically pertinent neural autoantibodies.
Patients, coworkers, and mice exposed to liquefied brain tissue had an autoantibody profile dominated by neural cation channel immunoglobulin Gs (IgGs). The most compelling link between patients and exposed mice was magnetic resonance imaging (MRI) evidence of grossly swollen spinal nerve roots. Autoantibody responses in patients and mice were dose-dependent and declined after antigen exposure ceased. Autoantibodies detected most frequently, and at high levels, bound to detergent-solubilized macromolecular complexes containing neuronal voltage-gated potassium channels ligated with a high affinity Kv1 channel antagonist, 125I-α-dendrotoxin. Exposed mice exhibited a behavioral phenotype consistent with potassium channel dysfunction recognized in drosophila with mutant ("shaker") channels: reduced sensitivity to isoflurane-induced anesthesia. Pathological and electrophysiological findings in patients supported peripheral nerve hyperexcitability over destructive axonal loss. The pain-predominant symptoms were consistent with sensory nerve hyperexcitability.
Our observations establish that inhaled neural antigens readily induce neurological autoimmunity and identify voltage-gated potassium channel complexes as a major immunogen.
检验下述假说，即通过吸入气溶胶化脑组织而诱发的自身免疫会导致美国中西部生猪屠宰场员工中暴发以感觉为主的多发性神经根神经病。
每周 5 天，通过鼻腔内滴注将液化脑组织递送至小鼠体内。分析暴露于脑组织中的小鼠、患者和未受影响的屠宰场员工的血清中是否存在具有临床相关性的神经自身抗体。
暴露于液化脑组织的患者、接触者和小鼠具有以神经阳离子通道免疫球蛋白 G（IgG）为主的自身抗体特征。患者和暴露于脑组织的小鼠之间最有力的联系是磁共振成像（MRI）显示的粗状肿胀的脊神经根。患者和小鼠的自身抗体反应呈剂量依赖性，并且在抗原暴露停止后下降。最常检测到的自身抗体，且水平较高，与含有神经元电压门控钾通道的去污剂可溶大分子复合物结合，该复合物与高亲和力 Kv1 通道拮抗剂 125I-α-二氢托品结合。暴露于脑组织的小鼠表现出与具有突变（“shaker”）通道的果蝇中钾通道功能障碍一致的行为表型：对异氟烷诱导的麻醉的敏感性降低。患者的病理和电生理发现支持周围神经兴奋性过高而非破坏性轴突丢失。以疼痛为主的症状与感觉神经兴奋性过高一致。
我们的观察结果证实，吸入的神经抗原可轻易诱导神经自身免疫，并确定电压门控钾通道复合物为主要免疫原。
