Background <p>IgA vasculitis (IgAV) is an autoimmune disorder characterized by inflammation of the small blood vessels. The pathogenesis of IgAV is believed to involve a complex interplay between immune cells, metabolites, and inflammatory cytokines (ICs).</p> Methods <p>We performed two-sample Mendelian randomization (MR) analysis to examine the causal relationship between immune cell traits, metabolites, ICs, and IgAV. Genetic variants associated with exposure, mediators and outcome were extracted from large-scale genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was used as the primary approach, supported by MR Egger, weighted median, simple mode, and weighted mode methods.</p> Results <p>In this study, we identified 25 immune cells, 6 metabolites (Threonate, Carnitine C5:1, Chiro-inositol, Carnitine C18:2, 3-formylindole, Cholate to phosphate ratio) and 2 ICs (T − cell surface glycoprotein CD5, Osteoprotegerin) associated with IgAV. Meanwhile, we identified 5 immune cell—metabolites—IgAV pathways (CD28⁺CD45RA⁻CD8dim AC—3-formylindole—IgAV; CD28⁺ CD45RA⁻ CD8dim AC—Cholate to phosphate ratio—IgAV; CD28⁺ CD45RA⁺ CD8br%T cell—3-formylindole—IgAV; CD25 on IgD⁺ CD38⁻ unswmem—Chiro-inositol- IgAV; HLA DR on CD14⁺ CD16⁻ monocyte—Chiro-inositol—IgAV; CD39⁺ secreting Treg %secreting Treg-Threonate—IgAV) and 4 immune cells—ICs—IgAV pathways (IgD⁻ CD38⁻ AC—Osteoprotegerin—IgAV; CD45 on T—Osteoprotegerin—IgAV; HLA DR on CD14⁺ CD16⁻ monocyte—CD5—IgAV; HLA DR on CD14⁺CD16⁻ monocyte—CD5—IgAV).</p> Conclusions <p>These results highlight the need for further research to investigate the underlying mechanisms and identify potential therapeutic targets for the treatment of IgAV.</p>