Rouvroye Maxine D, Warendorf Janna, Vrancken Alexander, Eftimov Filip, Wieske Luuk, Faber Catharina G, Hoeijmakers Janneke G J, Damoiseaux Jan, van de Warrenburg Bart, van Gaalen Judith, van der Molen Renate, Bouma Gerd, Bontkes Hetty
Department of Gastroenterology and Hepatology, AG&M Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, the Netherlands.
J Neurol. 2025 Jun 7;272(7):447. doi: 10.1007/s00415-025-13187-w.
Immune reactivity to gluten in the development of peripheral neuropathies and cerebellar ataxia has been suggested for decades, but evidence is scarce. The aim of the current study was to test the prevalence of tissue transglutaminase 2 (anti-TG2), tissue transglutaminase 6 (anti-TG6), and gliadin antibodies (anti-gliadin) in a large cross-sectional study. The sera of patients with idiopathic cerebellar ataxia, idiopathic small fibre neuropathy (SFN) and chronic idiopathic axonal polyneuropathy (CIAP), and controls with a comparable age distribution and men/women ratio were collected. The sera were analysed for anti-gliadin IgA/IgG (manufacturer's and lower cut-off), anti-TG2 IgA and anti-TG6 IgA/IgG. In total, 683 samples were analysed: 476 patients (249 SFN, 161 CIAP and 66 idiopathic cerebellar ataxia) and 195 controls. There were no differences between disease and control group in the prevalence of elevated anti-TG6, anti-TG2 and anti-gliadin using the manufacturer's cut-off. Using a lower cut-off of 3 U/mL, previously used by others for gluten-related neurological disorders, anti-gliadin IgA was positive in 20.8% patients vs 12.8% controls (p = 0.017) and anti-gliadin IgG in 7.6% vs 2.6% (p = 0.013), respectively. In subgroup analyses, significant differences were only observed in SFN for anti-gliadin IgA and in idiopathic cerebellar ataxia for anti-gliadin IgG using this lower cut-off after adjusting for sex and age. In conclusion, no difference in anti-TG2, anti-TG6 and anti-gliadin levels were observed between patients and controls. Only when using the lower cut-off (3 U/mL), the patients with SFN and idiopathic cerebellar ataxia were more often positive for anti-gliadin than controls. Whether these low-titre antibodies are gluten related, have any pathophysiological relevance, or reflect an epiphenomenon of neurodegeneration or gut inflammation is unknown.
数十年来，一直有人提出在周围神经病变和小脑共济失调的发展过程中存在对麸质的免疫反应，但证据稀少。本研究的目的是在一项大型横断面研究中检测组织转谷氨酰胺酶2（抗TG2）、组织转谷氨酰胺酶6（抗TG6）和麦醇溶蛋白抗体（抗麦醇溶蛋白）的患病率。收集了特发性小脑共济失调、特发性小纤维神经病变（SFN）和慢性特发性轴索性多发性神经病变（CIAP）患者以及年龄分布和男女比例相当的对照组的血清。对血清进行抗麦醇溶蛋白IgA/IgG（制造商设定值及更低临界值）、抗TG2 IgA和抗TG6 IgA/IgG分析。总共分析了683份样本：476例患者（249例SFN、161例CIAP和66例特发性小脑共济失调）和195例对照。使用制造商设定的临界值时，疾病组和对照组在抗TG6、抗TG2和抗麦醇溶蛋白升高的患病率方面没有差异。使用其他人先前用于麸质相关神经系统疾病的3 U/mL更低临界值时，抗麦醇溶蛋白IgA在20.8%的患者中呈阳性，而对照组为12.8%（p = 0.017），抗麦醇溶蛋白IgG在患者中为7.6%，对照组为2.6%（p = 0.013）。在亚组分析中，在调整性别和年龄后，仅在SFN中抗麦醇溶蛋白IgA以及在特发性小脑共济失调中抗麦醇溶蛋白IgG使用此更低临界值时观察到显著差异。总之，患者和对照组之间未观察到抗TG2、抗TG6和抗麦醇溶蛋白水平的差异。仅在使用更低临界值（3 U/mL）时，SFN患者和特发性小脑共济失调患者抗麦醇溶蛋白呈阳性的情况比对照组更常见。这些低滴度抗体是否与麸质相关、是否具有任何病理生理相关性，或者是否反映神经退行性变或肠道炎症的一种附带现象尚不清楚。
