Gut Microbiota, GdIgA1, and IgAN

IgA1 deposition is a hallmark of immunoglobulin A nephropathy (IgAN). Galactose-deficient IgA1 (GdIgA1) is crucial to the formation of these immunodeposits, but its origin is not understood. Few studies have shed light on the gut microbiota and conditions that spur GdIgA1 production, leading to IgAN.

Therefore, Li Gao and colleagues decided to analyze the fecal microbiome of patients with IgAN, focusing on their immune response to microbiota. The findings were published in Frontiers in Immunology.

The researchers performed 16S ribosomal RNA gene sequencing to compare IgAN samples to control samples from household-matched or nonrelated individuals. They measured levels of plasma GdIgA1 and poly-IgA complexes, and identified potential microbes that could incite IgA-directed antibody response or degrade IgA through specific IgA protease activities.

The fecal microbiota makeup of the IgAN group was distinctive from that of the controls. The IgAN group had a high quantity of Escherichia-Shigella based on analyses utilizing receiver operating characteristic (area under curve, 0.837; 95% CI, 0.738-0.914), principal coordinates, and the linear discriminant analysis effect size algorithm (linear discriminant analysis score, 4.56; P<.001).

The higher bacterial levels of IgAN patients corresponded with high titers of plasma GdIgA1 (r=0.36; P<.001). The IgAN group also had higher IgA1 against Shiga toxin type 2 (2.88±0.46 IU/mL vs 1.34±0.35 IU/mL; P=.03), the primary antigen of Escherichia-Shigella. Meanwhile, the healthy controls demonstrated a higher abundance of the commensal bacteria that produce IgA-degrading proteases. The abundance of certain intestinal bacteria expressing IgA proteases demonstrated an inverse correlation with the levels of plasma GdIgA1 in IgAN patients.

In conclusion, the findings suggest that Escherichia-Shigella exposure might encourage mucosal IgA production, including that of GdIgA1. Meanwhile, IgA protease-producing microbiota in the gut are suppressed in patients with IgAN, resulting in an overall reduction of GdIgA1 levels. “Thus,” the authors wrote, “our findings provide new perspective on the interplays among gut microbiome, mucosal infections, and mucosal immune responses during the onset and the progression of IgAN.”

Source: Frontiers in Immunology