Laboratory of Biochemistry, CHU Saint-Etienne, Saint-Etienne, France
Synaptopathies et autoanticorps (synatac), Institut Neuromyogène, Saint-Priest-en-Jarez, France.
J Neurol Neurosurg Psychiatry. 2020 Jan;91(1):49-57. doi: 10.1136/jnnp-2019-321849. Epub 2019 Nov 5.
Sensory neuropathies (SNs) are often classified as idiopathic even if immunological mechanisms can be suspected. Antibodies against the intracellular domain of the fibroblast growth factor receptor 3 (FGFR3) possibly identify a subgroup of SN affecting mostly the dorsal root ganglion (DRG). The aim of this study was to identify the frequency of anti-FGFR3 antibodies and the associated clinical pattern in a large cohort of patients with SN.
A prospective, multicentric, European and Brazilian study included adults with pure SN. Serum anti-FGRF3 antibodies were analysed by ELISA. Detailed clinical and paraclinical data were collected for each anti-FGFR3-positive patient and as control for anti-FGFR3-negative patients from the same centres ('center-matched').
Sixty-five patients out of 426 (15%) had anti-FGFR3 antibodies, which were the only identified autoimmune markers in 43 patients (66%). The neuropathy was non-length dependent in 89% and classified as sensory neuronopathy in 64%, non-length-dependent small fibre neuropathy in 17% and other neuropathy in 19%. Specific clinical features occurred after 5-6 years of evolution including frequent paresthesia, predominant clinical and electrophysiological involvement of the lower limbs, and a less frequent mixed large and small fibre involvement. Brazilians had a higher frequency of anti-FGFR3 antibodies than Europeans (36% vs 13%, p<0.001), and a more frequent asymmetrical distribution of symptoms (OR 169, 95% CI 3.4 to 8424).
Anti-FGFR3 antibodies occur in a subgroup of SN probably predominantly affecting the DRG. Differences between Europeans and Brazilians could suggest involvement of genetic or environmental factors.
感觉性神经病（SNs）通常被归类为特发性，即使免疫机制可能被怀疑。针对成纤维细胞生长因子受体 3（FGFR3）细胞内结构域的抗体可能确定了一个主要影响背根神经节（DRG）的 SN 亚组。本研究的目的是确定在大量 SN 患者中抗-FGFR3 抗体的频率及其相关临床模式。
一项前瞻性、多中心、欧洲和巴西研究纳入了单纯性 SN 的成年人。通过 ELISA 分析血清抗-FGRF3 抗体。对每个抗-FGFR3 阳性患者以及来自同一中心的抗-FGFR3 阴性患者（“中心匹配”）详细的临床和辅助检查数据进行收集。
在 426 例患者中，有 65 例（15%）患者有抗-FGFR3 抗体，其中 43 例（66%）患者为唯一自身免疫标志物。90%的神经病是非长度依赖性的，64%的患者被归类为感觉神经元病，17%的患者为非长度依赖性小纤维神经病，19%的患者为其他神经病。特定的临床特征在疾病进展 5-6 年后出现，包括频繁的感觉异常、下肢更常见的临床和电生理学受累，以及较少出现的混合大纤维和小纤维受累。巴西患者抗-FGFR3 抗体的频率高于欧洲患者（36%对 13%，p<0.001），且症状的不对称分布更为常见（比值比 169，95%置信区间 3.4 至 8424）。
抗-FGFR3 抗体存在于一个亚组的 SN 中，可能主要影响 DRG。欧洲人和巴西人之间的差异可能表明涉及遗传或环境因素。
