Causal association between peripheral immune cells and IgA nephropathy: a Mendelian randomization study

Area of Science:

• Immunology
• Nephrology
• Genetics

Background:

• The link between peripheral immune cells and immunoglobulin A nephropathy (IgAN) is recognized, but causal evidence is limited.
• Investigating the causal role of specific immune cells in IgAN is crucial for understanding disease pathogenesis.

Purpose of the Study:

• To determine the causal effect of peripheral immune cells, including total white blood cells and lymphocyte subsets, on IgAN risk.
• To explore the relationship between immune cell traits and IgAN using Mendelian randomization (MR).

Main Methods:

• Employed inverse-variance weighted (IVW) Mendelian randomization (MR) as the primary analytical method.
• Utilized complementary methods like weighted median, MR-Egger regression, and MR-PRESSO for pleiotropy assessment.
• Conducted multivariable MR (MVMR) adjusting for C-reactive protein (CRP) and bidirectional MR analyses.

Main Results:

• A potential causal relationship was found between higher lymphocyte counts and increased IgAN risk in European populations (OR: 1.43).
• This association persisted after adjusting for CRP levels (OR: 1.44).
• Significant associations were observed for specific immune cell counts and median fluorescence intensities, with CD3+ T cells showing a consistent positive correlation with IgAN.

Conclusions:

• Genetically determined high lymphocyte counts are causally associated with an increased risk of IgAN.
• Lymphocyte count represents a potential causal risk factor for immunoglobulin A nephropathy.
• The study provides robust genetic evidence supporting the role of lymphocytes in IgAN pathogenesis.