Research Institute of Neuromuscular and Neurodegenerative Diseases and Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Front Immunol. 2022 Jul 26;13:939062. doi: 10.3389/fimmu.2022.939062. eCollection 2022.
Autoimmune nodopathy with anti-contactin-1 (CNTN1) responds well to rituximab instead of traditional therapies. Although a low-dose rituximab regimen was administered to patients with other autoimmune diseases, such as myasthenia gravis and neuromyelitis optica spectrum disorders, and satisfactory outcomes were obtained, this low-dose rituximab regimen has not been trialed in anti-CNTN1-positive patients.
Anti-CNTN1 nodopathy patients were enrolled in this prospective, open-label, self-controlled pilot study. A cell-based assay was used to detect anti-CNTN1 antibodies and their subclasses in both serum and cerebrospinal fluid. Clinical features were evaluated at baseline, 2 days, 14 days, and 6 months after single low-dose rituximab treatment (600 mg). The titers of the subclasses of anti-CNTN1 antibody and peripheral B cells were also evaluated at baseline, 2 days, and 6 months after the rituximab regimen.
Two patients with anti-CNTN1 antibodies were enrolled. Both patients had neurological symptoms including muscle weakness, tremor, sensory ataxia, numbness and mild nephrotic symptoms. In the field of neurological symptoms, sensory ataxia markedly improved, and the titer of anti-CNTN1 antibody as well as CD19+ B cells decreased only two days following low-dose rituximab treatment. Other neurological symptoms improved within two weeks of rituximab treatment. At the 6-month follow-up, all neurological symptoms steadily improved with steroid reduction, and both the anti-CNTN1 antibody titer and CD19+ B cells steadily decreased. No adverse events were observed after this single low-dose rituximab treatment.
We confirmed the clinical efficacy of low-dose rituximab by B cell depletion in autoimmune nodopathy with anti-CNTN1 antibody. This rapid and long-lasting response suggests that low-dose rituximab is a promising option for anti-CNTN1 nodopathy.
抗接触蛋白-1（CNTN1）自身免疫性结节病对利妥昔单抗治疗反应良好，而不是传统疗法。虽然已经在重症肌无力和视神经脊髓炎谱系障碍等其他自身免疫性疾病患者中使用低剂量利妥昔单抗方案，但获得了令人满意的结果，但这种低剂量利妥昔单抗方案尚未在抗-CNTN1 阳性患者中进行试验。
本前瞻性、开放标签、自身对照的初步研究纳入了抗-CNTN1 结节病患者。使用基于细胞的测定法检测血清和脑脊液中的抗-CNTN1 抗体及其亚类。在单次低剂量利妥昔单抗治疗（600mg）后 2 天、14 天和 6 个月评估临床特征。在利妥昔单抗方案治疗后 2 天和 6 个月还评估了抗-CNTN1 抗体和外周 B 细胞亚类的滴度。
纳入了 2 例抗-CNTN1 抗体阳性患者。2 例患者均有神经系统症状，包括肌无力、震颤、感觉性共济失调、麻木和轻度肾病症状。在神经系统症状方面，感觉性共济失调明显改善，在低剂量利妥昔单抗治疗后仅两天，抗-CNTN1 抗体滴度和 CD19+B 细胞就下降了。其他神经系统症状在利妥昔单抗治疗两周内改善。在 6 个月的随访中，随着类固醇剂量减少，所有神经系统症状均稳定改善，抗-CNTN1 抗体滴度和 CD19+B 细胞也稳定下降。单次低剂量利妥昔单抗治疗后未观察到不良反应。
我们通过 B 细胞耗竭证实了低剂量利妥昔单抗治疗抗-CNTN1 抗体自身免疫性结节病的临床疗效。这种快速且持久的反应表明，低剂量利妥昔单抗是抗-CNTN1 结节病的一种有前途的选择。
Zotero 插件