Differential gut microbiota and inflammatory cytokines contribute to IgA vasculitis

Abstract

Objectives: Immunoglobulin A vasculitis (IgAV) is the most common form of vasculitis in childhood. Emerging evidence indicates that gut microbiota plays a key role in the pathogenesis of IgAV. However, the factors linking gut microbiota to the onset and progression of IgAV are poorly understood. We aimed to demonstrate that the presence of a specific dysbiosis in patients with IgAV contributes to the onset of IgAV.

Methods: We transplanted gut microbiota from human donors with IgAV or healthy controls (HCs). The changes in gut microbiota and serum indexes of the recipient mice were detected, and the IgAV-associated bacteria were determined by integrating the results from the mouse sequence data analysis with the human sequence results.

Results: 55 amplicon sequence variants (ASVs) specific to IgAV children were detected in the recipient IgAV microbiota (rIMb) mice, and 35 ASVs specific to healthy children were detected in the recipient healthy microbiota (rHMb) mice. Gut microbiota in rIMb mice differs from that in rHMb mice. Alcaligenaceae could discriminate rIMb from rHMb mice, while its abundance was decreased in rIMb compared to rHMb (p<0.05). In children with IgAV, the abundance of Burkholderiaceae (Alcaligenaceae accounted for 99.7%) at the family level was significantly lower compared to HCs, which can be used to distinguish children with IgAV from HCs, and the constructed receiver operating characteristic (ROC) curve had an area under the curve (AUC) value of 0.766. In addition, the rIMb group had a markedly higher interleukin (IL)-17A and IL-21 level than those in the rHMb group. The Spearman correlation analysis indicated significant correlations between the relative levels of these pro-inflammatory cytokines, IgA and alterations of gut microbiota.

Conclusions: IgAV is characterised by disturbances of gut microbiota composition and an imbalance in inflammatory cytokines. The manipulation of gut microbiota could be a possible way to prevent and manage IgAV.