Causal Associations Between Immune Cell Phenotypes and Oral Lichen Planus: A Large-Scale Mendelian Randomization...

Area of Science:

• Immunology
• Genetics
• Oral Medicine

Background:

• Oral lichen planus (OLP) is an inflammatory condition with complex etiology.
• Understanding the immune cell phenotypes causally associated with OLP susceptibility is crucial for developing targeted therapies.

Purpose of the Study:

• To systematically identify immune cell phenotypes causally associated with oral lichen planus (OLP) susceptibility using Mendelian randomization (MR).

Main Methods:

• A two-sample MR study evaluated causal relationships between 731 immune cell phenotypes and OLP risk.
• Single nucleotide polymorphisms (SNPs) were rigorously filtered and harmonized.
• Inverse variance weighting was the primary analysis method, with sensitivity analyses performed.

Main Results:

• Twenty-eight immune phenotypes showed significant causal associations with OLP: 19 protective and 9 risk-increasing.
• Regulatory T-cell (Treg) phenotypes, particularly CD3 on CD4 Tregs, were protective (OR=0.916).
• CD8-bright leukocytes showed the strongest risk association (OR=1.487), while certain B cell and monocyte phenotypes had mixed effects.

Conclusions:

• Genetic evidence suggests OLP pathogenesis involves an immunoregulatory imbalance.
• Findings support precision therapeutic strategies targeting specific immune pathways in OLP.
• The study offers insights applicable to other oral autoimmune diseases.