PDF(Pubmed)
Abstract：
The occurrence of immune-mediated diseases (IMDs) in amyotrophic lateral sclerosis (ALS) patients is widely reported. However, whether IMDs and ALS is a simple coexistence or if there exists causal relationships between the two has been a subject of great interest to researchers.
A total of 454,444 participants from the prospective cohort of UK Biobank were recruited to investigate the longitudinal association between IMDs and ALS. Previously any IMDs and organ specific IMDs were analyzed in relation to the following incident ALS by Cox-proportional hazard models. Subgroup analyses were performed to explore the covariates of these relationships.
After adjusting for potential covariates, the multivariate analysis showed that any IMDs were associated with an increased risk of ALS incidence (HR:1.42, 95%CI:1.03-1.94). IMDs of the endocrine-system and the intestinal-system were associated with increased risk of ALS incidence (endocrine-system IMDs: HR:3.01, 95%CI:1.49-6.06; intestinal system IMDs: HR:2.07, 95%CI: 1.14-3.77). Subgroup analyses revealed that immune burden, including IMD duration and the severity of inflammation had specific effects on the IMD-ALS association. In participants with IMD duration≥10 years or CRP≥1.3mg/L or females, previous IMDs increased the risk of incident ALS; however, in participants with IMD duration <10 years or CRP<1.3mg/L or males, IMDs had no effect on incident ALS.
Our study provides evidence that previous any IMDs and endocrine-system and the intestinal-system specific IMDs are associated with an increased risk of developing ALS in females, but not in males.
A total of 454,444 participants from the prospective cohort of UK Biobank were recruited to investigate the longitudinal association between IMDs and ALS. Previously any IMDs and organ specific IMDs were analyzed in relation to the following incident ALS by Cox-proportional hazard models. Subgroup analyses were performed to explore the covariates of these relationships.
After adjusting for potential covariates, the multivariate analysis showed that any IMDs were associated with an increased risk of ALS incidence (HR:1.42, 95%CI:1.03-1.94). IMDs of the endocrine-system and the intestinal-system were associated with increased risk of ALS incidence (endocrine-system IMDs: HR:3.01, 95%CI:1.49-6.06; intestinal system IMDs: HR:2.07, 95%CI: 1.14-3.77). Subgroup analyses revealed that immune burden, including IMD duration and the severity of inflammation had specific effects on the IMD-ALS association. In participants with IMD duration≥10 years or CRP≥1.3mg/L or females, previous IMDs increased the risk of incident ALS; however, in participants with IMD duration <10 years or CRP<1.3mg/L or males, IMDs had no effect on incident ALS.
Our study provides evidence that previous any IMDs and endocrine-system and the intestinal-system specific IMDs are associated with an increased risk of developing ALS in females, but not in males.
摘要：
■广泛报道了肌萎缩侧索硬化症（ALS）患者中免疫介导的疾病（IMD）的发生。然而,IMD和ALS是否简单共存，或者两者之间是否存在因果关系，一直是研究人员非常感兴趣的课题。
■从英国生物银行的前瞻性队列中招募了454,444名参与者，以调查IMD和ALS之间的纵向关联。以前，通过Cox比例风险模型分析了与以下事件ALS相关的任何IMD和器官特异性IMD。进行亚组分析以探索这些关系的协变量。
■调整潜在协变量后，多变量分析显示,任何IMD均与ALS发病率增加相关(HR:1.42,95CI:1.03~1.94).内分泌系统和肠道系统IMD与ALS发病风险增加相关(内分泌系统IMD:HR:3.01,95CI:1.49-6.06;肠道系统IMD:HR:2.07,95CI:1.14-3.77)。亚组分析显示，免疫负担，包括IMD持续时间和炎症严重程度对IMD-ALS关联有特定影响.在IMD持续时间≥10年或CRP≥1.3mg/L或女性的参与者中，以前的IMD增加了ALS事件的风险；然而，在IMD持续时间<10年或CRP<1.3mg/L或男性的参与者中，IMD对ALS事件没有影响。
我们的研究提供的证据表明，以前的任何IMD和内分泌系统以及肠道系统特异性IMD都与女性患ALS的风险增加有关。但不是男性。
■从英国生物银行的前瞻性队列中招募了454,444名参与者，以调查IMD和ALS之间的纵向关联。以前，通过Cox比例风险模型分析了与以下事件ALS相关的任何IMD和器官特异性IMD。进行亚组分析以探索这些关系的协变量。
■调整潜在协变量后，多变量分析显示,任何IMD均与ALS发病率增加相关(HR:1.42,95CI:1.03~1.94).内分泌系统和肠道系统IMD与ALS发病风险增加相关(内分泌系统IMD:HR:3.01,95CI:1.49-6.06;肠道系统IMD:HR:2.07,95CI:1.14-3.77)。亚组分析显示，免疫负担，包括IMD持续时间和炎症严重程度对IMD-ALS关联有特定影响.在IMD持续时间≥10年或CRP≥1.3mg/L或女性的参与者中，以前的IMD增加了ALS事件的风险；然而，在IMD持续时间<10年或CRP<1.3mg/L或男性的参与者中，IMD对ALS事件没有影响。
我们的研究提供的证据表明，以前的任何IMD和内分泌系统以及肠道系统特异性IMD都与女性患ALS的风险增加有关。但不是男性。
