Impact of Immune Cells on IgA Vasculitis via Metabolites and Inflammatory Cytokines.

BACKGROUND

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).

METHODS

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.

RESULTS

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).

CONCLUSIONS

These results highlight the need for further research to investigate the underlying mechanisms and identify potential therapeutic targets for the treatment of IgAV.