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Deciphering diabetic neuropathy: immune cell causality revealed.

Yunfeng Yu1,2, Xinyu Yang1, Yuman Yin1

  • 1School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.

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|September 1, 2025
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Summary

This Mendelian randomization study identified seven immune cell phenotypes causally linked to diabetic neuropathy (DN). These findings highlight potential immune targets for DN, requiring further validation.

Keywords:
Immune cellsMendelian randomizationcausalitydiabetic neuropathygenome-wide association studyphenotype

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Area of Science:

  • Immunology
  • Genetics
  • Neurology

Background:

  • Diabetic neuropathy (DN) is a common complication of diabetes mellitus.
  • Understanding the genetic underpinnings of DN is crucial for developing effective treatments.
  • Immune cell phenotypes play a role in the pathogenesis of various diseases, including diabetic complications.

Purpose of the Study:

  • To investigate the causal relationship between specific immune cell phenotypes and the genetic susceptibility to diabetic neuropathy (DN).
  • To utilize Mendelian randomization (MR) analysis to assess these causal effects.
  • To identify potential immune markers associated with DN risk.

Main Methods:

  • Employed Mendelian randomization (MR) analysis using genetic data for immune cell phenotypes and DN.
  • Utilized datasets from the European Bioinformatics Institute and FinnGen.
  • Performed stepwise selection of single nucleotide polymorphisms (SNPs) and employed inverse variance weighted (IVW) as the primary analytical tool.
  • Assessed horizontal pleiotropy, heterogeneity, and robustness using MR-Egger intercept, Cochran's Q test, and leave-one-out analyses.

Main Results:

  • MR analysis identified seven immune cell phenotypes significantly associated with increased genetic susceptibility to DN.
  • Specific phenotypes include CD24+CD27+ %lymphocyte, CD24+CD27+ AC, CD28-CD127-CD25++CD8br %T cell, CD28-CD25++CD8br AC, CD33-HLA DR - AC, CD8 on CM CD8br, and naïve CD4+ %CD4+.
  • Sensitivity analyses confirmed the absence of significant horizontal pleiotropy and heterogeneity, supporting the robustness of the findings.

Conclusions:

  • Seven distinct immune cell phenotypes demonstrate a causal association with genetic susceptibility to diabetic neuropathy.
  • These findings provide preliminary evidence for the role of specific immune cell profiles in DN pathogenesis.
  • Further experimental validation in diverse populations is warranted to confirm the clinical significance of these immune cell phenotypes in DN.