Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

The mechanisms underlying the complex correlation between immunoglobulin A nephropathy (IgAN) and inflammatory bowel disease (IBD) remain unclear. This study aimed to identify the optimal cross-talk genes, potential pathways, and mutual immune-infiltrating microenvironments between IBD and IgAN to elucidate the linkage between patients with IBD and IgAN. The IgAN and IBD datasets were obtained from the Gene Expression Omnibus (GEO). Three algorithms, CIBERSORTx, ssGSEA, and xCell, were used to evaluate the similarities in the infiltrating microenvironment between the two diseases. Weighted gene co-expression network analysis (WGCNA) was implemented in the IBD dataset to identify the major immune infiltration modules, and the Boruta algorithm, RFE algorithm, and LASSO regression were applied to filter the cross-talk genes. Next, multiple machine learning models were applied to confirm the optimal cross-talk genes. Finally, the relevant findings were validated using histology and immunohistochemistry analysis of IBD mice. Immune infiltration analysis showed no significant differences between IBD and IgAN samples in most immune cells. The three algorithms identified 10 diagnostic genes, MAPK3, NFKB1, FDX1, EPHX2, SYNPO, KDF1, METTL7A, RIDA, HSDL2, and RIPK2; FDX1 and NFKB1 were enhanced in the kidney of IBD mice. Kyoto Encyclopedia of Genes and Genomes analysis showed 15 mutual pathways between the two diseases, with lipid metabolism playing a vital role in the cross-talk. Our findings offer insights into the shared immune mechanisms of IgAN and IBD. These common pathways, diagnostic cross-talk genes, and cell-mediated abnormal immunity may inform further experimental studies.</p

A Genetic Variant rs1801274 in <i>FCGR2A</i> as a Potential Risk Marker for Kawasaki Disease: A Case-Control Study and Meta-Analysis

<div><p>Objectives</p><p>Recent genome-wide association study found rs1801274, a functional single nucleotide polymorphism (SNP) in IgG receptor gene <i>FCGR2A</i>, was associated with increased risk of Kawasaki disease (KD). However, subsequent studies on the role of this SNP were limited and controversial.</p><p>Methods</p><p>A case-control study was conducted in a Chinese Han population including 428 KD patients and 493 controls to examine the association between rs1801274 and KD susceptibility. A meta-analysis was performed in combination with the relevant published studies to further clarify such an association.</p><p>Results</p><p>Our case-control study found that rs1801274 was significantly associated with increased risk of KD in the Chinese Han population, with an odds ratio (OR) of 1.58 (95% CI = 0.96–2.62) for the GA genotype and 1.93 (95% CI = 1.16–3.19) for the AA genotype compared with the GG genotype. The result of meta-analysis further demonstrated that the A allele of rs1801274 was significantly correlated with KD risk under the allelic model (OR = 1.35, 95% CI = 1.27–1.44) without heterogeneity by fixed-effects model analysis (<i>Q</i> = 17.30, <i>p</i> = 0.139). Moreover, sensitivity analysis supported the robustness of this meta-analysis.</p><p>Conclusion</p><p>These results further confirm that rs1801274 in the <i>FCGR2A</i> gene is significantly associated with increased risk of KD.</p></div

Flow chart of study selection.

<p>Flow chart of study selection.</p

Characteristics of the studies on rs1801274 polymorphisms and risk of Kawasaki disease included in the meta-analysis.

<p>Abbreviations: CC, Case Control; TDT, transmission/disequilibrium test; T, transmission; NT, non-transmission.</p

<i>FCGR2A</i> rs1801274 allele A and the risk of Kawasaki disease in meta-analysis.

a<p>Fixed-effects OR, <i>Q</i> = 17.30, <i>P</i>_{heterogeneity} = 0.139, <i>p</i><0.001.</p

The funnel plot of natural logarithm of OR against inverse standard error in each study.

<p>Regression test for funnel plot asymmetry <i>p</i> = 0.224.</p

The forest plot for the association between the A allelic variant and the risk of Kawasaki disease.

<p>For each study, the estimate of OR and its 95% CI is plotted with a box and a horizontal line. Fixed-effects pooled OR = 1.35, 95% CI = 1.27–1.44, <i>p</i><0.001; <i>Q</i> = 17.30, <i>P</i>_{heterogeneity} = 0.139.</p

Polymorphism of rs1801274 of the <i>FCGR2A</i> gene in the KD patients and healthy controls in current study.

a<p>Adjusted the effect of gender and age. KD, Kawasaki disease.</p>b<p>The values in bold indicate statistically significant (<i>p</i><0.05).</p

The characteristics of patients with Kawasaki disease and healthy controls in current study.

a<p><i>P</i> value was calculated by χ² test.</p

The mRNA expression level of <i>YAP1</i> gene in all four populations of the HapMap cell lines.

<p>The mRNA expression level of <i>YAP1</i> gene in all four populations of the HapMap cell lines.</p