The peripheral immune cell counts and mouth ulcers: A two-sample Mendelian randomization study

Area of Science:

• Immunology
• Genetics
• Oral Medicine

Background:

• Mouth ulcers (MUs) are common oral lesions with multifactorial etiology.
• The role of peripheral immune cell profiles in MU development remains incompletely understood.
• Host immune factors are implicated in the pathogenesis of MUs.

Purpose of the Study:

• To investigate the causal association between peripheral immune cell counts and the risk of developing mouth ulcers (MUs).
• To utilize a two-sample Mendelian Randomization approach to assess genetic associations.
• To identify specific immune cell types that causally influence MU susceptibility.

Main Methods:

• Employed two-sample Mendelian Randomization (MR) analysis.
• Utilized summary statistics from large genome-wide association studies (GWAS).
• Assessed 12 circulating immune cell types and one ratio (CD4+/CD8+) as exposures and MUs as the outcome, primarily using the inverse-variance weighted (IVW) method and sensitivity analyses for pleiotropy.

Main Results:

• Inverse-variance weighted (IVW) analysis revealed a protective causal effect of higher leukocyte counts (OR=0.93, P=0.0115) and lymphocyte counts (OR=0.91, P=0.0150) against MUs.
• Wald ratio analysis indicated that higher CD4+ T-cell counts causally reduce MU risk (OR=0.70, P=1.05×10⁻²⁰), whereas higher CD8+ T-cell counts causally increase MU risk (OR=1.25, P=9.99×10⁻²¹).
• Sensitivity analyses did not indicate significant horizontal pleiotropy.

Conclusions:

• Peripheral immune cell counts have a significant causal effect on the incidence of mouth ulcers.
• Elevated leukocyte, lymphocyte, and CD4+ T-cell counts are associated with a reduced risk of MUs, suggesting a protective immune role.
• Conversely, increased CD8+ T-cell counts are causally linked to an elevated risk of MUs, underscoring the complex interplay of immune responses in MU pathogenesis.