Service de Neurologie, CHU de Saint-Etienne, Saint-Etienne, France Université de Saint-Etienne Jean Monnet, Saint-Etienne, France Centre de Référence Maladies Neuromusculaires Rares, CHU de Saint-Etienne, Saint-Etienne, France Centre de Référence Français des Syndromes Neurologiques Paraneoplasiques, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France Lyon Centre de Recherche de Neuroscience INSERM U1028/CNRS UMR 5292, Lyon, France.
Université de Saint-Etienne Jean Monnet, Saint-Etienne, France Lyon Centre de Recherche de Neuroscience INSERM U1028/CNRS UMR 5292, Lyon, France. Laboratoire de Biochimie, CHU de Saint-Etienne, Saint-Etienne, France.
J Neurol Neurosurg Psychiatry. 2015 Dec;86(12):1347-55. doi: 10.1136/jnnp-2014-309730. Epub 2015 Jan 27.
Immunological mechanisms are suspected in sensory neuropathy (SN) occurring with systemic autoimmune diseases and in some idiopathic cases, but so far there are no antibodies (Abs) identifying these neuropathies.
In the search for such specific antibodies, serum samples were collected from 106 patients with SN of these 72 fulfilled the diagnosis criteria of sensory neuronopathy (SNN) and 211 control subjects including patients with sensorimotor neuropathies, other neurological diseases (ONDs), systemic autoimmune diseases and healthy blood donors.
In the first step, a protein array with 8000 human proteins allowed identification of the intracellular domain of the fibroblast growth factor receptor 3 (FGFR3) as a target of Abs in 7/16 SNN and 0/30 controls. In the second step, an ELISA method was used to test the 317 patients and controls for anti-FGFR3 Abs. Abs were detected in 16/106 patients with SN and 1/211 controls (p<0.001). Among the 106 patients with SN, anti-FGFR3 Abs were found in 11/38 patients with autoimmune context, 5/46 with idiopathic neuropathy and 0/22 with neuropathy of other aetiology (p=0.006). The only control patient with anti-FGFR3 Abs had lupus and no recorded neuropathy. Sensitivity, specificity, and positive and negative predictive values of anti-FGFR3 Abs for a diagnosis of idiopathic or dysimmune SN were 19%, 99.6%, 94.1% and 77.3%, respectively. A cell-based assay confirmed serum reactivity against the intracellular domain of FGFR3. The neuropathy in patients with anti-FGF3 Abs was non-length dependent in 87% of patients and fulfilled the criteria of probable SNN in 82%. Trigeminal nerve involvement and pain were frequent features.
A anti-FGFR3 Abs identify a subgroup of patients with SN in whom an underlying autoimmune disorder affecting sensory neurons in the dorsal root and trigeminal nerve ganglia is suspected.
免疫机制被怀疑与全身性自身免疫性疾病相关的感觉神经病变（SN）和一些特发性病例有关，但迄今为止，还没有能够识别这些神经病变的抗体（Abs）。
为了寻找这些特定的抗体，我们从 106 名 SN 患者的血清样本中进行了研究，其中 72 名患者符合感觉神经元病（SNN）的诊断标准，211 名对照者包括感觉运动性神经病、其他神经系统疾病（ONDs）、全身性自身免疫性疾病和健康献血者。
在第一步中，一个包含 8000 个人类蛋白的蛋白质阵列鉴定出成纤维细胞生长因子受体 3（FGFR3）的细胞内结构域是 16/16 例 SNN 和 0/30 例对照者的 Abs 靶标。在第二步中，我们使用 ELISA 方法检测了 317 名患者和对照者的抗 FGFR3 Abs。在 106 名 SN 患者中发现 16 例 Abs，在 211 名对照者中发现 1 例（p<0.001）。在 106 例 SN 患者中，自身免疫背景下 11/38 例、特发性神经病 5/46 例和其他病因的神经病 0/22 例患者存在抗 FGFR3 Abs（p=0.006）。唯一患有抗 FGFR3 Abs 的对照者患有狼疮且没有记录的神经病。抗 FGFR3 Abs 对特发性或免疫性 SN 的诊断的敏感性、特异性、阳性预测值和阴性预测值分别为 19%、99.6%、94.1%和 77.3%。细胞基础测定证实了血清对 FGFR3 细胞内结构域的反应性。抗 FGFR3 Abs 患者的神经病在 87%的患者中无长度依赖性，符合可能的 SNN 标准在 82%的患者中符合。三叉神经受累和疼痛是常见特征。
抗 FGFR3 Abs 可识别出一组 SN 患者，其中怀疑存在影响背根和三叉神经节感觉神经元的潜在自身免疫性疾病。
