J Clin Immunol. 2025 Nov 10;45(1):157. doi: 10.1007/s10875-025-01946-3.

ABSTRACT

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.

PMID:41207983 | DOI:10.1007/s10875-025-01946-3