Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Amyotroph Lateral Scler Frontotemporal Degener. 2021 May;22(3-4):211-219. doi: 10.1080/21678421.2020.1861022. Epub 2020 Dec 17.
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. 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. 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. 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.
为了评估 43 种自身免疫性疾病与随后发生肌萎缩侧索硬化症（ALS）的风险之间的关联，并进一步评估家族性混杂因素对这些关联的贡献。我们进行了一项全国性基于登记的巢式病例对照研究，纳入了 1990 年至 2013 年间在瑞典诊断的 3561 名 ALS 患者和 35610 名随机从一般人群中选择的对照者，且按照年龄、性别和出生地与病例进行个体匹配。为了评估家族因素对研究关联的贡献，我们还研究了 ALS 患者的一级亲属（兄弟姐妹和子女）及其对照者。与对照者相比，ALS 患者先前被诊断为自身免疫性疾病的风险高出 47%（OR 1.47，95%置信区间 [CI] 1.31-1.64）。几种自身免疫性疾病，包括重症肌无力、多发性肌炎或皮肌炎、格林-巴利综合征、30 岁以下诊断的 1 型糖尿病、多发性硬化症和甲状腺功能减退症，与 ALS 之间存在正相关。在 ALS 诊断前的一年中，任何自身免疫性疾病的风险增加最大，这可能是由于误诊。在 ALS 诊断前 2-5 年也观察到了统计学上显著增加的风险，但更早之前没有。然而，与对照组的一级亲属相比，ALS 患者的一级亲属没有自身免疫性疾病的风险增加。尽管很难完全消除误诊的潜在影响，但自身免疫性疾病（如 1 型糖尿病和多发性硬化症）与 ALS 之间可能存在正相关，这不能完全用共同的家族混杂因素来解释。
