RESUMO
Both IgA nephropathy (IgAN) and lupus nephritis (LN) are immunity-related diseases with a complex, polygenic, and pleiotropic genetic architecture. However, the mechanism by which the genetic variants impart immunity or renal dysfunction remains to be clarified. In this study, using gene expression datasets as a quantitative readout of peripheral blood mononuclear cell (PBMC)- and kidney-based molecular phenotypes, we analyzed the similarities and differences in the patterns of gene expression perturbations associated with the systematic and kidney immunity in IgAN and LN. Original gene expression datasets for PBMC, glomerulus, and tubule from IgAN and systemic lupus erythematosus (SLE) patients as well as corresponding controls were obtained from the Gene Expression Omnibus (GEO) database. The similarities and differences in the expression patterns were detected according to gene differential expression. Weighted gene co-expression network analysis (WGCNA) was used to cluster and screen the co-expressed gene modules. The disease correlations were then identified by cell-specific and functional enrichment analyses. By combining these results with the genotype data, we identified the differentially expressed genes causatively associated with the disease. There was a significant positive correlation with the kidney expression profile, but no significant correlation with PBMC. Three co-expression gene modules were screened by WGCNA and enrichment analysis. Among them, blue module was enriched for glomerulus and podocyte (P < 0.05) and positively correlated with both diseases (P < 0.05), mainly via immune regulatory pathways. Pink module and purple module were enriched for tubular epithelium and correlated with both diseases (P < 0.05) through predominant cell death and extracellular vesicle pathways, respectively. In genome-wide association study (GWAS) enrichment analysis, blue module was identified as the high-risk gene module that distinguishes LN from SLE and contains PSMB8 and PSMB9, the susceptibility genes for IgAN. In conclusion, IgAN and LN showed different systematic immunity but similarly abnormal immunity in kidney. Immunological pathways may be involved in the glomerulopathy and cell death together with the extracellular vesicle pathway, which may be involved in the tubular injury in both diseases. Blue module may cover the causal susceptibility gene for IgAN and LN.
RESUMO
Background: Mucosal immunity plays an important role in the pathogenesis of IgA nephropathy (IgAN). This study aimed to investigate if infection of Helicobacter pylori (H. pylori), a common bacteria in the gastrointestinal tract, associated with IgAN.Methods: This study included 261 patients with IgAN and 46 healthy controls. Clinical information and plasma samples were collected from patients and healthy controls. H. pylori infection was confirmed by western blot. Plasma IgA1 and galactose-deficient IgA1 (Gd-IgA1) levels were detected by specific enzyme-linked immunosorbent assay.Results: Total H. pylori infection rates showed no statistical differences between IgAN patients and healthy controls, but the infection rates of type I H. pylori in IgAN patients were significantly higher than those in healthy controls (44.4 vs. 28.3%, p = 0.040). Compared with uninfected patients, the systolic blood pressure, 24-h proteinuria, and blood urea nitrogen levels were significantly higher in patients with H. pylori infection (126.0 ± 15.5 vs. 119.6 ± 14.5 mmHg, p = 0.010; 1.8 ± 2.7 vs. 1.2 ± 1.4 g/24h, p = 0.013; 7.9 ± 5.4 vs. 6.7 ± 3.9 µmol/L, p = 0.042), especially in patients with type I infection (126.5 ± 15.4 vs. 119.6 ± 14.5 mmHg, p = 0.002; 1.9 ± 2.9 vs. 1.2 ± 1.4 g/24 h, p = 0.033; 8.1 ± 5.6 vs. 6.7 ± 3.9 µmol/L, p = 0.041). Similarly, patients with IgAN and type I H. pylori infection showed higher plasma Gd-IgA1 levels than uninfected patients (5.5 ± 2.2 vs. 4.5 ± 2.2 µg/mL, p = 0.037).Conclusions: Virulent type I H. pylori infection is more common in patients with IgAN. Patients with IgAN and type I H. pylori infection showed lower renal function and higher underglycosylation of plasma IgA1.