Bidirectional associations between eosinophils, basophils, and lymphocytes with atopic dermatitis: A multivariable...

Area of Science:

• Immunology
• Genetics
• Dermatology

Background:

• Observational studies suggest associations between basophils, eosinophils, lymphocytes, and atopic dermatitis (AD).
• The causal role of these immune cells in AD pathogenesis remains unclear.
• Potential confounding factors and reverse causation limit observational findings.

Purpose of the Study:

• To investigate the causal relationship between immune cell counts and atopic dermatitis (AD) risk.
• To differentiate direct and total effects of immune cell variations on AD.
• To leverage large-scale genetic data for robust causal inference.

Main Methods:

• Utilized single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR).
• Employed genetic data from UK Biobank and Blood Cell Consortium (>500,000 subjects).
• Validated findings across three independent AD cohorts (>700,000 subjects).

Main Results:

• Higher genetically predicted eosinophil and basophil counts were associated with increased AD risk (ORs > 1).
• Higher genetically predicted lymphocyte counts were associated with decreased AD risk (OR < 1).
• MVMR confirmed these independent causal effects of eosinophils, basophils, and lymphocytes on AD.

Conclusions:

• Mendelian randomization findings suggest a causal link between specific immune cell counts and AD.
• Increased eosinophil and basophil levels, and decreased lymphocyte levels, are identified as potential causal risk factors for AD.
• These immune cell variations represent independent risk factors for atopic dermatitis development.