Abstract

Objective: To assess the associations of 43 autoimmune diseases with the subsequent risk of ALS and further evaluate the contribution of familial confounding to these associations.

Methods: We conducted a nationwide register-based nested case-control study including 3561 ALS patients diagnosed during 1990–2013 in Sweden and 35,610 controls that were randomly selected from the general population and individually matched to the cases on age, sex, and county of birth. To evaluate the contribution of familial factors on the studied association, we additionally studied the first-degree relatives (siblings and children) of ALS patients and their controls.

Results: Patients with ALS had a 47% higher risk of being previously diagnosed with autoimmune disease (OR 1.47, 95% confidence interval [CI] 1.31–1.64), compared with controls. A positive association was noted for several autoimmune diseases, including myasthenia gravis, polymyositis or dermatomyositis, Guillain-Barre syndrome, type 1 diabetes diagnosed younger than 30 years, multiple sclerosis, and hypothyreosis. The increased risk of any autoimmune disease was greatest during the year before ALS diagnosis, likely due to misdiagnosis. A statistically significantly increased risk was also noted during 2–5 years, but not earlier, before ALS diagnosis. First-degree relatives of ALS patients had however no increased risk of autoimmune diseases compared with first-degree relatives of controls.

Conclusions: Although it is difficult to completely remove the potential effects of misdiagnosis, there is likely a positive association between autoimmune disease (such as type 1 diabetes and multiple sclerosis) and ALS, which is not fully explained by shared familial confounding factors.

摘要

目的：评估43种自身免疫性疾病与随后的ALS风险的关联，并进一步评估家族混杂因素对这些关联的贡献。

方法：我们在全国范围内进行了基于登记的嵌套病例对照研究，研究对象包括1990年至2013年在瑞典诊断的3561名ALS患者和35610名从总人群中随机选择的，分别与年龄，性别和县级匹配的病例。出生。为了评估家族因素对所研究关联的贡献，我们还研究了ALS患者及其对照的一级亲属（兄弟姐妹和儿童）。

结果：与对照组相比，ALS患者先前被诊断出患有自身免疫性疾病的风险高47％（OR 1.47，95％置信区间[CI] 1.31-1.64）。与几种自身免疫性疾病呈正相关，包括重症肌无力，多肌炎或皮肌炎，格林-巴利综合征，诊断为30岁以下的1型糖尿病，多发性硬化症和甲状腺功能低下症。在ALS诊断之前的一年中，任何自身免疫性疾病的风险增加最大，可能是由于误诊所致。在ALS诊断之前的2-5年内（但没有更早），还注意到统计学上显着增加的风险。然而，与对照的一级亲属相比，ALS患者的一级亲属没有增加自身免疫性疾病的风险。

结论：尽管很难完全消除误诊的潜在影响，但自身免疫性疾病（例如1型糖尿病和多发性硬化症）与ALS之间可能存在正相关，但不能由共同的家庭混杂因素充分解释。