Polygenic associations and causal inferences between serum immunoglobulins and amyotrophic lateral sclerosis

Chen, Xu; Shen, Xiaojun; Zhang, Xuzhuo; Zhan, Yiqiang; Fang, Fang

doi:10.1016/j.cca.2021.07.007

Cited by 3 publications

(1 citation statement)

References 24 publications

(24 reference statements)

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“…However, some studies have shown that although elevated neutrophils or monocytes are associated with lower Amyotrophic Lateral Sclerosis Functional Rating Scale -revised (ALSFRS-R) score, there is no association between it and ALS progression (Cui et al, 2022). Similarly, there is controversy over the levels of immunoglobulins and complement in the serum of ALS patients (Chen et al, 2021;Lo and Lee, 2021;Wang et al, 2021). This suggests that the peripheral immune status in ALS may be related to the disease process and thus requires further study.…”

Section: Introductionmentioning

confidence: 99%

Peripheral immune markers and amyotrophic lateral sclerosis: a Mendelian randomization study

Hu,

Zuo,

Mao

et al. 2023

Front. Neurosci.

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IntroductionThe peripheral immune system changes in amyotrophic lateral sclerosis (ALS), but the causal relationship between the two is still controversial.MethodsIn this study, we aimed to estimate the causal relationship between peripheral immune markers and ALS using a two-sample Mendelian randomization method. Genome-wide association study (GWAS) data on peripheral blood immune traits from European populations were used for exposure, and ALS summary statistics were used as the outcome. The causal relationship was evaluated by inverse variance weighting, MR-Egger, and weighted median methods and verified by multiple sensitivity analysis.ResultsWe found that the increase of one standard deviation of lymphocyte count is related to reducing ALS risk. CD3 on effector memory CD4+ T cell, HLA DR+ CD4+ T cell, effector memory CD8+ T cell, terminally differentiated CD8+ T cell and CD28- CD8+ T cell is also a protective factor for ALS. Among the circulating immune protein, the increase of one standard deviation of α-2-macroglobulin receptor-associated protein (α-2-MRAP) and C4b showed associated with low risk of ALS, while Interleukin-21 (IL-21) increases the risk of ALS.DiscussionOur study further reveals the important role of peripheral immune activity in ALS.

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