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Causal association between the peripheral immunity and the risk and disease severity of multiple sclerosis

Lian Chen1,2, Li-Fang Zhu1,2, Lu-Yang Zhang1,2

  • 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Frontiers in Immunology
|February 23, 2024
PubMed
Abstract

Insights

This study found that higher counts of white blood cells and lymphocytes genetically increase the risk of Multiple Sclerosis (MS). Conversely, certain T cell subsets and IL-2Ra levels show a protective effect against MS development.

Area of Science:

  • Immunology
  • Genetics
  • Neurology

Background:

  • Multiple Sclerosis (MS) is an autoimmune disease with complex immunological underpinnings.
  • Specific immune system factors contributing to MS risk and severity remain incompletely understood.

Purpose of the Study:

  • To investigate the causal associations between peripheral hematological traits and Multiple Sclerosis (MS) risk and severity.
  • To identify specific immune cell counts, cytokines, and growth factors influencing MS pathogenesis.

Main Methods:

  • Mendelian randomization (MR) analysis was employed to assess genetic associations.
  • Subgroup analyses were conducted on immune cell counts and circulating factors.
  • Odds ratios (OR) with 95% confidence intervals (CI) and adjusted p-values were calculated.

Main Results:

  • Elevated white blood cell and lymphocyte counts were genetically linked to increased MS risk.
  • Higher absolute counts of T cells and CD4+ T cells were associated with greater MS risk.
  • Increased CD25++CD4+ T cells and CD25++CD8+ T cells demonstrated a protective effect against MS.
  • Elevated Interleukin-2 receptor alpha (IL-2Ra) levels were detrimental to MS risk.
  • Associations between CD4+ T cell traits, regulatory T cells (Tregs), and MS severity were suggested.

Conclusions:

  • Genetic predisposition to higher peripheral immune cell counts causally influences MS risk.
  • Specific immune cell subsets, including regulatory T cells and T cell populations expressing CD25, play distinct roles in MS.
  • These findings offer potential targets for understanding MS mechanisms and developing future therapies.
Keywords:
Mendelian randomization (MR)cytokinesgenome wide association study (GWAS)multiple sclerosisperipheral immune cells

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