Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank

ObjectiveThe 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.MethodsA to...

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Main Authors: Wen Cao, Zhi Cao, Lu Tang, Chenjie Xu, Dongsheng Fan
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-03-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1356132/full
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author Wen Cao
Wen Cao
Zhi Cao
Zhi Cao
Lu Tang
Lu Tang
Chenjie Xu
Dongsheng Fan
Dongsheng Fan
author_facet Wen Cao
Wen Cao
Zhi Cao
Zhi Cao
Lu Tang
Lu Tang
Chenjie Xu
Dongsheng Fan
Dongsheng Fan
author_sort Wen Cao
collection DOAJ
description ObjectiveThe 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.MethodsA 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.ResultsAfter 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.InterpretationOur 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.
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spelling doaj.art-b048ce714d4842fcaf83fc3dea02256a2024-03-05T04:59:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13561321356132Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK BiobankWen Cao0Wen Cao1Zhi Cao2Zhi Cao3Lu Tang4Lu Tang5Chenjie Xu6Dongsheng Fan7Dongsheng Fan8Department of Neurology, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Disorders, Beijing, ChinaSchool of Public Health, Zhejiang University School of Medicine, Hangzhou, ChinaSchool of Public Health, Hangzhou Normal University, Hangzhou, ChinaDepartment of Neurology, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Disorders, Beijing, ChinaSchool of Public Health, Hangzhou Normal University, Hangzhou, ChinaDepartment of Neurology, Peking University Third Hospital, Beijing, ChinaBeijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Disorders, Beijing, ChinaObjectiveThe 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.MethodsA 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.ResultsAfter 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.InterpretationOur 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1356132/fullamyotrophic lateral sclerosisIMDUK Biobankimmunityprospective cohort
spellingShingle Wen Cao
Wen Cao
Zhi Cao
Zhi Cao
Lu Tang
Lu Tang
Chenjie Xu
Dongsheng Fan
Dongsheng Fan
Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank
Frontiers in Immunology
amyotrophic lateral sclerosis
IMD
UK Biobank
immunity
prospective cohort
title Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank
title_full Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank
title_fullStr Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank
title_full_unstemmed Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank
title_short Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank
title_sort immune mediated diseases are associated with a higher risk of als incidence a prospective cohort study from the uk biobank
topic amyotrophic lateral sclerosis
IMD
UK Biobank
immunity
prospective cohort
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1356132/full
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