Genetically predicted associations between circulating cytokines and autoimmune diseases: a bidirectional two-sample...

Area of Science:

• Immunology
• Genetics
• Epidemiology

Background:

• Cytokine involvement in autoimmune diseases is known but causality is unclear.
• Autoimmune diseases such as Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE), and Hashimoto's Thyroiditis (HT) pose significant health burdens.
• Understanding the etiological factors of autoimmune diseases is crucial for developing effective interventions.

Purpose of the Study:

• To investigate the causal relationships between genetically predicted levels of 91 cytokines and the risk of MS, SLE, and HT.
• To identify potential cytokine biomarkers for early diagnosis and prevention strategies.
• To explore novel cytokine associations with autoimmune disease pathogenesis.

Main Methods:

• A bidirectional two-sample Mendelian Randomization (MR) approach was employed.
• Utilized large-scale genetic datasets for MS, SLE, and HT, alongside cytokine data from 14,824 participants.
• Employed inverse variance weighted, weighted median, and MR-Egger methods, with sensitivity analyses for robustness.

Main Results:

• Identified specific cytokines causally associated with decreased risk of MS (e.g., IL-18, ADA, SCF).
• Revealed several cytokines linked to increased or decreased SLE risk (e.g., IL-4, IL-7, IL-10RA, CXCL5, NTN, FGF23, MCP4).
• Found associations between cytokines (e.g., CDCP1, IL-33, TRAIL) and HT risk, and implicated others in disease development.

Conclusions:

• Established causal links between specific cytokines and the risk of MS, SLE, and HT.
• Highlighted potential utility of identified cytokines as biomarkers for disease diagnosis and prevention.
• Uncovered novel cytokine associations, paving the way for future research into autoimmune disease mechanisms and therapeutics.