Bresciani Lorenzo, Salvalaggio Alessandro, Vegezzi Elisa, Visentin Andrea, Fortuna Andrea, Anglani Mariagiulia, Cacciavillani Mario, Masciocchi Stefano, Scaranzin Silvia, Carecchio Miryam, Martinuzzi Andrea, Gastaldi Matteo, Briani Chiara
Department of Neurosciences, University of Padova, Padova, Italy.
IRCCS Mondino Foundation, Pavia, Italy.
J Peripher Nerv Syst. 2023 Sep;28(3):522-527. doi: 10.1111/jns.12565. Epub 2023 Jun 3.
Nodopathies and paranodopathies are autoimmune neuropathies associated with antibodies to nodal-paranodal antigens (neurofascin 140/186 and 155, contactin-1, contactin-associated protein 1 [Caspr1]) characterized by peculiar clinical features, poor response to standard immunotherapies (e.g., intravenous immunoglobulins, IVIg). Improvement after anti-CD20 monoclonal antibody therapy has been reported. Data on Caspr1 antibodies pathogenicity are still preliminary, and longitudinal titers have been poorly described.
We report on a young woman who developed a disabling neuropathy with antibodies to the Caspr1/contactin-1 complex showing a dramatic improvement after rituximab therapy, mirrored by the decrease of antibody titers.
A 26-year-old woman presented with ataxic-stepping gait, severe motor weakness at four limbs, and low frequency postural tremor. For neurophysiological evidence of demyelinating neuropathy, she was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy and treated with IVIg without benefit. MRI showed symmetrical hypertrophy and marked signal hyperintensity of brachial and lumbosacral plexi. Cerebrospinal fluid showed 710 mg/dL protein. Despite intravenous methylprednisolone, the patient progressively worsened, and became wheelchair-bound. Antibodies to nodal-paranodal antigens were searched for by ELISA and cell-based assay. Anticontactin/Caspr1 IgG4 antibodies resulted positive. The patient underwent rituximab therapy with slow progressive improvement that mirrored the antibodies titer, measured throughout the disease course.
Our patient had a severe progressive course with early disability and axonal damage, and slow recovery starting only a few months after antibody-depleting therapy. The close correlation between titer, disability, and treatment, supports the pathogenicity of Caspr1 antibodies, and suggest that their longitudinal evaluation might provide a potential biomarker to evaluate treatment response.
结旁神经病和结旁周围神经病是与结旁抗原（神经束蛋白140/186和155、接触蛋白-1、接触蛋白相关蛋白1 [Caspr1]）抗体相关的自身免疫性神经病，具有独特的临床特征，对标准免疫疗法（如静脉注射免疫球蛋白，IVIg）反应不佳。已有报道抗CD20单克隆抗体治疗后病情改善。关于Caspr1抗体致病性的数据仍属初步，且纵向滴度的描述较少。
我们报告了一名年轻女性，她患有一种致残性神经病，伴有针对Caspr1/接触蛋白-1复合物的抗体，在利妥昔单抗治疗后病情显著改善，抗体滴度下降。
一名26岁女性表现为共济失调步态、四肢严重运动无力和低频姿势性震颤。由于有脱髓鞘性神经病的神经生理学证据，她被诊断为慢性炎症性脱髓鞘性多发性神经根神经病，并接受IVIg治疗但无改善。MRI显示臂丛和腰骶丛对称肥大且信号明显高增强。脑脊液显示蛋白含量为710mg/dL。尽管使用了静脉注射甲泼尼龙，患者病情仍逐渐恶化，最终需依靠轮椅行动。通过酶联免疫吸附测定（ELISA）和基于细胞的检测方法检测结旁抗原抗体。抗接触蛋白/Caspr1 IgG4抗体呈阳性。患者接受了利妥昔单抗治疗，病情缓慢逐渐改善，这与在整个病程中测量的抗体滴度情况相符。
我们的患者病程严重且进展性，早期出现残疾和轴索损伤，在抗体清除治疗几个月后才开始缓慢恢复。滴度、残疾程度和治疗之间的密切相关性支持了Caspr1抗体的致病性，并表明对其进行纵向评估可能提供一种评估治疗反应的潜在生物标志物。
