Visser Anne E, Pazoki Raha, Pulit Sara L, van Rheenen Wouter, Raaphorst Joost, van der Kooi Anneke J, Ricaño-Ponce Isis, Wijmenga Cisca, Otten Henny G, Veldink Jan H, van den Berg Leonard H
Department of Neurology, Brain Center Rudolf Magnus, F02.230, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
Department of Epidemiology and Biostatistics, MRC-PHE Center for Environment and Health, School of Public Health, Imperial College London, London, UK.
J Neurol. 2017 Apr;264(4):694-700. doi: 10.1007/s00415-017-8400-8. Epub 2017 Feb 6.
To examine evidence for a role of gluten sensitivity (GS) or celiac disease (CD) in ALS etiology, we included participants from a population-based case-control study in The Netherlands between January 2006 and December 2015. We compared levels and seroprevalence of IgA antibodies to tissue transglutaminase 6 (TG6) in 359 ALS patients and 359 controls, and to transglutaminase 2 (TG2) and endomysium (EMA) in 199 ALS patients and 199 controls. Questionnaire data on 1829 ALS patients and 3920 controls were examined for CD or gluten-free diets (GFD). Genetic correlation and HLA allele frequencies were analyzed using two genome-wide association studies: one on ALS (12,577 cases, 23,475 controls), and one on CD (4533 cases, 10,750 controls). We found one patient with TG6, TG2 and EMA antibodies who had typical ALS and no symptoms of GS. TG6 antibody concentrations and positivity, CD prevalence and adherence to a GFD were similar in patients and controls (p > 0.66) and in these patients disease progression was compatible with typical ALS. CD and ALS were not found to be genetically correlated (p > 0.37). CD-associated HLA allele frequencies were similar in patients and controls (p > 0.28). In conclusion, we found no serological evidence for involvement of gluten-related antibodies in ALS etiology nor did we observe an association between CD and ALS in medical history or genetic data, indicating that there is no evidence in our data for an association between the two diseases. Hence, a role for a GFD in the ALS treatment seems unlikely.
为了研究麸质敏感性（GS）或乳糜泻（CD）在肌萎缩侧索硬化症（ALS）病因学中的作用，我们纳入了2006年1月至2015年12月期间荷兰一项基于人群的病例对照研究中的参与者。我们比较了359例ALS患者和359例对照中抗组织转谷氨酰胺酶6（TG6）的IgA抗体水平和血清阳性率，以及199例ALS患者和199例对照中抗转谷氨酰胺酶2（TG2）和抗肌内膜（EMA）的IgA抗体水平和血清阳性率。我们检查了1829例ALS患者和3920例对照关于CD或无麸质饮食（GFD）的问卷数据。使用两项全基因组关联研究分析了遗传相关性和HLA等位基因频率：一项针对ALS（12577例病例，23475例对照），另一项针对CD（4533例病例，10750例对照）。我们发现1例同时具有TG6、TG2和EMA抗体的患者，其患有典型的ALS且无GS症状。患者和对照中的TG6抗体浓度及阳性率、CD患病率和对GFD的依从性相似（p>0.66），并且在这些患者中疾病进展与典型ALS相符。未发现CD和ALS存在遗传相关性（p>0.37）。患者和对照中的CD相关HLA等位基因频率相似（p>0.28）。总之，我们未发现血清学证据表明麸质相关抗体参与ALS病因学，在病史或遗传数据中也未观察到CD与ALS之间存在关联，这表明我们的数据中没有证据支持这两种疾病之间存在关联。因此，GFD在ALS治疗中似乎不太可能发挥作用。
