Elucidating Causal Associations Between Immune Cells, Circulating Inflammatory Proteins, and Chronic Inflammatory...

Area of Science:

• Immunology
• Genetics
• Neurology

Background:

• Immune cells and inflammatory proteins are implicated in chronic inflammatory demyelinating polyneuropathy (CIDP) pathogenesis.
• Causal links between these factors and CIDP require further investigation.

Purpose of the Study:

• To explore causal associations between immune cell traits, inflammatory proteins, and CIDP using a two-sample, two-step Mendelian randomization (MR) approach.

Main Methods:

• Genome-wide association studies data from large European cohorts were utilized.
• Two-sample MR analysis, including fixed-effect inverse variance weighted and Bayesian-weighted MR, assessed associations.
• Sensitivity analyses were performed to ensure robustness and investigate potential pleiotropy.

Main Results:

• Twenty-five immune cell traits showed significant associations with CIDP risk, with 17 increasing risk and 8 being protective.
• Cystatin D (CST5) and interleukin-18 (IL-18) were identified as inflammatory proteins linked to CIDP.
• Partial mediation by CST5 between CD8+ NKT %T cells and CIDP was observed, though not statistically significant.

Conclusions:

• Novel interactions between immune cells, inflammatory proteins, and CIDP have been identified.
• These findings offer potential new immune targets for developing future CIDP therapies.